publicdata/cancer-gov
1
0
Fork 0
Code Issues Pull requests Projects Releases Packages Wiki Activity Actions
cancer-gov/chornobyltissuebank.cancer.gov/research/research_projects/index.html
Scott Williams 8c20e7076a Initial commit
2025-02-25 20:59:21 -05:00

2308 lines
182 KiB
HTML
Raw Blame History

This file contains invisible Unicode characters

This file contains invisible Unicode characters that are indistinguishable to humans but may be processed differently by a computer. If you think that this is intentional, you can safely ignore this warning. Use the Escape button to reveal them.

<!--
Copyright 2023, Institute for Systems Biology
Licensed under the Apache License, Version 2.0 (the "License");
you may not use this file except in compliance with the License.
You may obtain a copy of the License at
http://www.apache.org/licenses/LICENSE-2.0
Unless required by applicable law or agreed to in writing, software
distributed under the License is distributed on an "AS IS" BASIS,
WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
See the License for the specific language governing permissions and
limitations under the License.
-->
<!DOCTYPE html>
<html lang="en" class="no-js h-100">
<head>
<meta charset="utf-8">
<meta http-equiv="x-ua-compatible" content="ie=edge">
<title>
Chernobyl Tissue Bank | Research Projects Using CTB Materials
</title>
<meta name="description" content="
Research Projects Using CTB Materials
">
<meta name="viewport" content="width=device-width, initial-scale=1">
<meta name="google-site-verification" content="G8FxanvJ2mU-zIC9bSs8UjEkGUib3T8Z6HW2Nd_-kBM" />
<link rel="icon" type="image/x-icon" href="/static/img/favicon.ico"/>
<link type="text/css" rel="stylesheet" href="/static/css/style.css"/>
<!-- Global site tag (gtag.js) - Google Analytics -->
<script async
src="https://www.googletagmanager.com/gtag/js?id=G-E4QHZZVN8G"></script>
<script>
window.dataLayer = window.dataLayer || [];
function gtag() {
dataLayer.push(arguments);
}
gtag('js', new Date());
gtag('config', 'G-E4QHZZVN8G');
</script>
<script>
let STATIC_FILES_URL = '/static/';
let BASE_URL = 'https://chornobyltissuebank.cancer.gov' || "";
let search_tissue_samples_url = "/search_facility/search_samples/search_tissue_samples";
let filter_tissue_samples_url = "/search_facility/search_samples/filter_tissue_samples";
let clinical_search_facility_url = "/search_facility/search_samples/clinical_search_facility";
let search_clinical_url = "/search_facility/search_samples/search_clinical";
let delete_filters_url = "/search_facility/delete_filters/0/";
let driver_search_facility_url = "/search_facility/search_samples/driver_search_facility";
let open_summary_url = "/search_facility/open_file/submission_id/1/";
let open_application_url = "/search_facility/open_file/submission_id/0/";
let get_search_list_url = "/search_facility/get_search_list/";
let get_submissions_list_url = "/search_facility/get_submissions_list/";
let save_filters_url = "/search_facility/save_filters";
</script>
</head>
<body class="content h-100 d-flex flex-column" id="body">
<!--Include site main header-->
<div class="fixed-top bg-white shadow">
<nav id="ctb-main-navbar" class="navbar navbar-expand-xl navbar-light" aria-label="Main navigation">
<div class="container-lg my-2 justify-content-between">
<div class="d-none d-lg-inline-block">
<a class="navbar-brand ps-0" href="/">
<img class="me-2"
src="/static/img/ctb-nci-logo.svg"
height="50px" alt="nci-logo"></a>
</div>
<div class="d-lg-none d-inline-block">
<a class="navbar-brand ps-0" href="/"><img
src="/static/img/ctb-nci-logo.svg"
height="35px" alt="nci-logo"></a>
</div>
<div class="d-xl-none d-inline-block">
<button class="d-xl-none d-inline-block btn me-3 collapsed" type="button" id="SearchBarCollapse"
data-bs-toggle="collapse"
data-bs-target=".ctb-search-bar-collapsible"
aria-label="Toggle search bar">
<i class="fas fa-search"></i>
</button>
<button class="navbar-toggler border-0 btn collapsed" type="button" id="navbarSideCollapse"
data-bs-toggle="collapse"
data-bs-target="#ctb-collapsible-navbar"
aria-label="Toggle navigation">
<i class="fs-4 fas fa-bars"></i>
</button>
</div>
<div class="collapse container px-0 d-xl-none ctb-search-bar-collapsible" id="ctb-search-bar">
<form action="/ctb_search" method="get" role="search" class="d-flex">
<div class="input-group my-3">
<input type="text" class="form-control" name="q" placeholder=""
aria-label="Search CTB" aria-describedby="button-search">
<button class="btn btn-primary" type="submit" id="button-search">Search
</button>
</div>
</form>
</div>
<div class="navbar-collapse collapse justify-content-between ms-5" id="ctb-collapsible-navbar">
<ul class="navbar-nav">
<li class="nav-item">
<a class="nav-link "
href="/about/">About</a>
</li>
<li class="nav-item">
<a class="nav-link active "
href="/research/">Research and Data Access</a>
</li>
<li class="nav-item">
<a class="nav-link "
aria-current="page"
href="/search_facility/dashboard/">
Search the Biorepository
</a>
</li>
</ul>
<div class="navbar-nav">
<li class="nav-item d-none d-xl-inline-block">
<a class="nav-link btn me-3 collapsed" type="button" id="SearchBarCollapse2"
data-bs-toggle="collapse"
data-bs-target=".ctb-search-bar-collapsible"
aria-label="Toggle search bar">
<i class="fas fa-search"></i>
</a>
</li>
<li class="nav-item">
<a class="nav-link "
href="/account/login/">
<i class="fas fa-sign-in-alt"></i><span class="sr-only">Sign-In</span>
</a>
</li>
</div>
</div>
</div>
</nav>
<div class="d-none d-xl-block">
<div class="collapse container ctb-search-bar-collapsible" id="ctb-search-bar2">
<div class="row justify-content-end">
<div class="col-lg-4 col-md-6 col">
<form action="/ctb_search" method="get" role="search" class="d-flex">
<div class="input-group mb-3">
<input type="text" class="form-control" name="q"
aria-label="Search by Keyword" aria-describedby="button-search">
<button class="btn btn-primary" type="submit" id="button-search">Search
</button>
</div>
</form>
</div>
</div>
</div>
</div>
</div>
<main id="research_projects" class="main-content content">
<div class="page-heading">
<div class="container-lg mt-4">
<nav style="--bs-breadcrumb-divider: '>';" aria-label="breadcrumb">
<ol class="breadcrumb">
<li class="breadcrumb-item"><a href="/">CTB</a></li>
<li class="breadcrumb-item"><a href="/research/">Research and CTB Data Access</a></li>
<li class="breadcrumb-item active" aria-current="page">Research Projects Using CTB Materials</li>
</ol>
</nav>
</div>
</div>
<div class="container-fluid">
<!-- Site Messages -->
<div class="row">
<div id="js-messages"></div>
</div>
<!-- Page Content -->
<div class="container-lg">
<div class="row my-3 d-flex justify-content-center">
<div class="col-lg-10 px-md-4">
<div id="research_projects" class="pt-3">
<h3 class="pt-3">Research Projects Using CTB Materials</h3>
</div>
<div class="mt-3">
<p>Please select one of the sections below to view a breakdown of the research projects:</p>
<div class="accordion accordion-flush" id="accordionFlushResearch">
<div class="accordion-item">
<h2 class="accordion-header">
<button class="accordion-button collapsed" type="button" data-bs-toggle="collapse"
data-bs-target="#flush-collapseOne" aria-expanded="false"
aria-controls="flush-collapseOne">
Research Projects: 2001-2009
</button>
</h2>
<div id="flush-collapseOne" class="accordion-collapse collapse"
data-bs-parent="#accordionFlushResearch">
<div class="accordion-body">
<ul>
<li>[001/2001] Expression profiling of tyrosine kinase genes in malignant
tumors of the thyroid gland.
<div><span class="fw-light">Heinz-Ulrich Weier, LBNL,
University of California, Berkeley</span> <a class="ms-2"
href="mailto:ugweier@lbl.gov"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c01" aria-expanded="false"
aria-controls="c01">
View Summary
</button>
</p>
<div class="collapse" id="c01">
<div class="card card-body">
<p>
Abnormal
expression of tyrosine kinase (tk)
genes is a common phenomenon in papillary thyroid carcinomas
(PTCs),
where it is believed to alter
cell growth and response to external signals such as growth
factors,
hormones etc. While the
pathogenesis of radiation-induced PTC remains unclear, there is
evidence
that tk genes such as the
receptor tyrosine kinases ret and NTRK-1 are abnormally
expressed,
and
that the overexpression of
some tk genes due to gene amplification or changes in gene
regulation in
the absence of structural
alterations may lead to oncogenic transformation of cells. Using
a
DNA
microarray based technique,
we have identified several tk genes with abnormal expression in
human
tumor cell lines. We now
propose to apply the technique to measure the relative
expression
levels
of more than 50 tk genes in
the PTC's that arose after the Chernobyl nuclear accident and to
compare
these expression profiles
with the gene expression pattern found in sporadic PTC cases and
tumors
that arose following low
level therapeutic irradiation of the thyroid. Results from this
study
may allow the identification
of molecular markers that can be used to facilitate tumor
diagnosis
and
staging, and, eventually,
provide targets for therapeutic intervention.</p>
</div>
</div>
</li>
<li>[002/2001] Chernobyl, an Integrated Pan-European Study, morphology,
oncogenes,
DNA repair and outcome in radiation carcinogenesis.
<div>
<span class="fw-light">GA Thomas, South West Wales Cancer Institute, University of Wales, Swansea,
UK.</span> <a href="mailto:gerry@mynydd-p.u-net.com" class="ms-2"><i class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c02" aria-expanded="false"
aria-controls="c02">
View Summary
</button>
</p>
<div class="collapse" id="c02">
<div class="card card-body">
<p>
The objective of this study is to
investigate the link between exposure of children to radiation,
the
subsequent development of
tumors and how their morphology, molecular and cell biology
influence
clinical outcome. The project
is an integrated approach involving 5 leading European centers.
Samples
of the same tumors will be
studied by the 5 different centers to determibe tumor morphology
and
type; the degree of variation
within the tumor, including the variation of the proportion of
cells
in
cycle using antibodies to
novel DNA replication associated peptides; the gene involved in
the
carcinogenic process, using DNA
chip technology; specific studies of the pathways associated
with
one
oncogene (ret) known to be
linked to the tumor type involved; and studies of novel gene
rearrangements using FISH technology.
By using the same tumor/normal pairs in these studies,
integrating
the
results from the different
centers and studies and correlating these with detailed
morphological
analysis and patient details
including evidence on tumor aggressiveness and recurrence, we
will
increase our understanding of
the link between radiation exposure and cancer development, and
provide
evidence which will inform
decisions on radiation protection and on clinical management of
patients
with radiation associated
cancers.</p>
</div>
</div>
</li>
<li>[004/2001] RET proto-oncogene rearrangements and tyrosine kinase gene
expression
in radiation induced papillary thyroid carcinomas developed after the
Chernobyl
accident.
<div>
<span class="fw-light">Horst Zitzelsberger, GSF, Munich, Germany</span>
<a
href="mailto:zitzelsberger@gsf.de" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c04" aria-expanded="false"
aria-controls="c04">
View Summary
</button>
</p>
<div class="collapse" id="c04">
<div class="card card-body">
<p>
The papillary thyroid
carcinoma oncogene (RET/PTC) is a rearranged version of the
tyrosine
kinase RET. It is know that the
incidence of RET/PTC activation is increased in
radiation-induced
papillary thyroid carcinomas
compared to papillary thyroid carcinomas without a radiation
history.
The prognostic value of
RET/PTC rearrangements and its importance as a
radiation-specific
marker
is still unclear. It is
proposed to screen 70 childhood cases from Belarus and Ukraine
with
interphase FISH in conjunction
with RT-PCR to confirm the presence and type of the chimeric
transcripts. Cases with indications for
atypical RET/PTC rearrangements will be further investigated
using
5'RACE for the presence of novel
types of alteration. For this part of the proposal RNA samples
as
well
as a limited number of
paraffin-embedded sections would be needed. The RNA samples will
be
further investigated for
expression profiles of other tyrosine kinase genes to identify
other
gene rearrangements which may
occur as a sole abnormality or in addition to RET/PTC
rearrangements.</p>
</div>
</div>
</li>
<li>[005/2001] Mitochondrial DNA deletions and mutations in post Chernobyl
thyroid
tumors and in the respective normal thyroid parenchyma.
<div>
<span class="fw-light">Manuel Sobrinho-Simoes, IPATIMUP, Porto, Portugal</span>
<a
href="mailto:sobrinho.simoes@ipatimup.pt" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c05" aria-expanded="false"
aria-controls="c05">
View Summary
</button>
</p>
<div class="collapse" id="c05">
<div class="card card-body">
<p>
Mittochondrial DNA (mtDNA) is a likely hotspot for mutation in
cancer as
it is preferentially modified by many carcinogens. We have
previously
shown that there is a specific association between sequence
variants
of
Complex I genes and ATPase6, one of the two mitochondrial genes
of
Complex V, and the occurrence of malignancy and of oxyphil
features
in
thyroid tumors. We have also found a significant association
between
mitochondrial sequence variants and the occurrence (and degree)
of
the
so-called mitochondrial common deletion. In an attempt to
elucidate
the
role of post-Chernobyl irradiation in mtDNA alterations and to
find
out
whether or not such alterations are involved in the
etiopathogenesis
of
thyroid tumors we will search for the mtDNA common deletion and
for
somatic mutations and sequence variants in the D-loop region, in
the
13
coding genes and in the 22 tRNAs genes of cases from which there
are
RNA
and DNA samples extracted from blood (set without radiation),
normal
thyroid (set irradiation) and tumors (set irradiation and
tumorigenesis). In a first step, we will study exhaustively 20
cases.
The results obtained in this first part will be used together
with
the
data we and others have previously obtained to decide the most
appropriate targets for the second part of the study. If
possible we
would like to correlate the results of our study on mtDNA
deletions
and
mutations with those on ret oncogene. In case there are also
clinico-pathyological data available, we would like to
collaborate
with
the pathologists who have studied the cases in order to clarify
the
putative clinical significance of the mtDNA alterations.</p>
</div>
</div>
</li>
<li>[007/2001] Expression of the RET proto-oncogene in post-Chernobyl thyroid
tumors
and unirradiated controls: analysis of RET/PTC rearrangements, RET wild type
and
RET-TK domain, with quantitative assessment of mRNA and protein expression.
<div>
<span class="fw-light">Aldo Pinchera, University of Pisa, Italy</span>
<a
href="mailto:a.pinchera@endoc.med.unipi.it" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c07" aria-expanded="false"
aria-controls="c07">
View Summary
</button>
</p>
<div class="collapse" id="c07">
<div class="card card-body">
<p>
Genetic alterations of the ret proto-oncogene play a critical
role
in
the pathogenesis of papillary thyroid carcinomas both naturally
occurring and radiation induced. We have recently found that
classical
RET/PTC rearrangements are present also in benign thyroid
nodular
disease. Furthermore, in several cases the independent
expression of
tyrosine kinase (TK) and extracellular (EC) domains of RET was
found.
This finding may be interpreted as RET wild type gene
expression. In
other cases, especially radiation exposed, the TK domain in the
absence
of EC was found and was interpreted as unknown RET/PTC
rearrangements
(PTCX). Aim of this project is to clarify the modality of
expression
of
RET protooncogene in nodular thyroid diseases. In cases with EC
and
TK
expression, we will search for RET wild type by an extralong PCR
encompassing the TK and EC domains, followed by sequencing of
the
PCR
product. In cases of TK positive expression only (but not
classical
PTC1, PTC2 and PTC3) we will identify the 5' domain rearranged
with
the
TK domain. As for other unknown RET/PTC rearrangements will use
the
5'race approach.</p>
<p>
All samples positive for TK expression will be submitted to
quantitative PCR (ABI Prism 7700 sequence detector, Perkin
Elmer)
for TK
mRNA. The TK mRNA expression will be correlated with the
histological
characteristics of the analysed tissues, and the
immunohistochemical
pattern of RET protein expression, using an antibody to
recognize
the TK
domain.</p>
</div>
</div>
</li>
<li>[001/2002] Analysis of RET/PTC transforming ability in Thyroid cells using
Oligonucleotide DNA Micro Array.
<div>
<span class="fw-light">Giuliana Salvatore, University of Naples, Italy</span>
<a
href="mailto:gsalvato@unina.it" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0102" aria-expanded="false"
aria-controls="c0102">
View Summary
</button>
</p>
<div class="collapse" id="c0102">
<div class="card card-body">
The expression of RET/PTC oncogenes in thyroid PC Cl 3 cells induces
a
complex phenotype with a block of the differentiation program,
hormone-independent proliferation and increased apoptotic rate.
Oligonucleotide GeneChips were used to analyse gene expression
profiles
of PC Cl 3 cells expressing either RET/PTC1 or RET/PTC3 oncogenes in
comparison to parental cells. About 2,000 genes showing at least
two-fold increase and 2,000 genes showing at least two-fold decrease
were identified in RET/PTC-expressing thyrocytes. Virtually all the
genes up-regulated by more than 5-folds (about 100) were confirmed
by
RT-PCR and some of them by immunoblot. Genes upregulated by RET/PTC
could be functionally divided in genes involved in proliferation
(such
as D-type cyclins), apoptosis, proteolysis, inflammation, and
metabolism. We plan to extend these studies on the identified genes
up
and on the downregulated by analyzing their expression in human
thyroid
tumors of different histotypes. We propose to study their expression
by
semiquantitative reverse transcriptase PCR and for selected genes by
real time quantitative PCR. Immunohistochemical analysis will be use
to
verify protein expression.
<br>
<br>
The findings of these studies can reveal clues to the molecular
pathways
involved in papillary thyroid carcinoma and may provide biomarkers
for
clinical use.
</div>
</div>
</li>
<li>[002/2002] A Comprehensive Molecular Profile of ChildhoodRadiation Induced
Papillary Thyroid Tumors Compared to Adult Sporadic Papillary Tumors.
<div>
<span class="fw-light">Lesleyann Hawthorn, Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York, USA</span>
<a href="mailto:lesleyann-hawthorn@roswellpark.org" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0202" aria-expanded="false"
aria-controls="c0202">
View Summary
</button>
</p>
<div class="collapse" id="c0202">
<div class="card card-body">
Papillary thyroid carcinoma (PTC) accounts for 80% of all thyroid
malignancies. It has a variable disease course and to date no
pathways
or specific genes have been implicated as causative in this tumor.
RET
activation, through translocations involving several genes, have
been
noted in a high incidence of PTCs. However, the activation of this
oncogene is found at all stages from benign through
well-differentiated
to undifferentiated carcinoma. This suggests that it represents an
early
event and that this defect is not in itself sufficient for
carcinogenesis. It may also suggest that the classification of PTC
covers more than one tumor subtype. The relationship between
radiation
exposure and PTC is well established. We plan to perform a genome
wide
scan using microarray analysis for alterations in tumors from
children
exposed to radiation and compare them to sporadic adult tumors to
identify which genes are commonly altered and which genes are
display
differential alteration expression patterns. We plan to extend this
study using high-resolution BAC-CGH to define a molecular pattern
for
these tumors and evaluate this approach for diagnostic applications.
The
study of molecular alterations which cause thyroid carcinoma is of
importance since the identification of causative factors could lead
to
new approaches for treatment.
</div>
</div>
</li>
<li>[001/2003] A comprehensive analysis to find out molecular biomarker(s) of
radiation exposure and grade of malignancy in human post-Chernobyl PTC
<div>
<span class="fw-light">Hiroyuki Namba, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan</span>
<a href="mailto:namba@net.nagasaki-u.ac.jp" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0103" aria-expanded="false"
aria-controls="c0103">
View Summary
</button>
</p>
<div class="collapse" id="c0103">
<div class="card card-body">
Development of papillary thyroid cancer (PTC), similarly to that of
most
of other human malignancies, is likely to comprise a multistep and
multihit process. It is quite probable that mutational events
initiating, promoting and/or driving the tumor progression are quite
similar in the sporadic and radiation-induced PTC. Along with this,
one
may expect there may be unidentified to date molecular distinctive
features peculiar to thyroid cancers of different etiology. Thus, a
comparative study of various molecular characteristics in the two
groups
of PTC may provide additional information for the determination of
the
molecular signature of radiation-induced thyroid cancerogenesis.
<br><br>
In the proposed project we intend to study the following molecular
characteristics of the DNA extractedfrom normal and tumor tissue of
radiation-induced PTCs: i) relative content of mtDNA and number of
large-scale deletions in mtDNA; ii) prevalence of gene mutations of
MAPK
signal molecules, including the Ras,BRAF, Raf-1 and MEK genes; and
iii)
distribution of the codon 72 allelic variants of theTP53.
<br><br>
After the data are obtained, we will perform a comprehensive
univariate
and multivariate statistical analysis against already available
results
of examination of sporadic PTC in order to identify molecular
parameter(s) specific to radiation-induced PTC.
</div>
</div>
</li>
<li>[002/2003] Molecular Change and Thyroid Cancer Risk after Chernobyl
<div>
<span class="fw-light">Scott Davis, Fred Hutchinson Cancer Centre, Seattle, USA</span>
<a href="mailto:sdavis@fhcrc.org" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0203" aria-expanded="false"
aria-controls="c0203">
View Summary
</button>
</p>
<div class="collapse" id="c0203">
<div class="card card-body">
This study investigates the occurrence and molecular characteristics
of
thyroid cancer in residents of the Bryansk Oblast of the Russian
Federation, who were 0-50 years of age at the time of exposure to
radiation from the Chernobyl Power Station accident (ATA) on April
26,
1986. The study has three primary purposes: 1) to characterize cases
of
thyroid cancer according to specific molecular markers of genetic
change, and investigate whether the presence of such markers is
associated with individual thyroid radiation dose from the Chernobyl
accident; 2) to investigate whether age-at-exposure dependent
radiation
dose response for thyroid cancer differs between cancers that are
positive versus negative for the molecular markers investigated; and
3)
to investigate whether the presence of these same molecular markers
is
associated with clinical outcomes. Included will be thyroid cancer
cases
diagnosed between April 1, 2001 and March 31, 2006 and confirmed by
a
panel of expert thyroid pathologists. An equal number of controls
will
be individually matched to cases by sex, age, type of settlement and
raion of residence on April 26, 1986. Data collected will include
in-person interviews for all participants, and for cases only,
paraffin
embedded tissue or fresh frozen tissue, clinical history and outcome
information.
</div>
</div>
</li>
<li>[001/2004] Analysis of Genetic and Epigenetic Abnormalities in
Radiation-induced
Thyroid Cancers
<div>
<span class="fw-light">Michael M Xing, John Hopkins University School of Medicine, Baltimore USA</span>
<a href="mailto:mxing1@jhmi.edu" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0104" aria-expanded="false"
aria-controls="c0104">
View Summary
</button>
</p>
<div class="collapse" id="c0104">
<div class="card card-body">
Thyroid cancers are the most common endocrine malignancies and the
vast
majority of them are papillary thyroid cancers (PTC). Several
genetic
abnormalities, including Ras mutations and RET/PTC rearrangements
have
been well characterized in these cancers. Recently, we and several
other
groups have reported the BRAF mutation in PTC with a high
prevalence. We
have also characterized aberrant DNA methylation in several genes in
thyroid cancers, including novel tumor suppressor genes and some
thyroid-specific genes. Except for the RET/PCT rearrangements, these
genetic and epigenetic abnormalities have been studied mainly in
sporadic thyroid cancers, and their role is unknown in the special
group
of thyroid cancers induced by radiation, the most common and
well-established environmental risk factor for thyroid cancer.
Chernobyl
nuclear accident has been associated with a significant increase in
the
incidence of PTC, which represent an ideal thyroid tumor model for
the
study of radiation-induced thyroid tumorigenesis. In the present
project, we propose to use such special thyroid cancer samples to
study
novel genetic and epigenetic abnormalities, their relationship, and
their effects on the expression of key thyroid genes.
Well-established
experimental protocols and techniques, including RT-PCR,
methylation-specific PCR, real-time quantitative PCR, and a recently
established colorimetric mutation detection method will be used. The
study is expected to result in important insights into
radiation-induced
thyroid tumorigenesis and provide novel clinical implications for
this
special group of thyroid cancers.
</div>
</div>
</li>
<li>[002/2004] Investigation of molecular genetic abnormalities associated with
progression of human thyroid follicular neoplasms
<div>
<span class="fw-light">D Wynford-Thomas, University of Wales College of Medicine, Cardiff UK</span>
<a href="mailto:kingTD@cardiff.ac.uk" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0204" aria-expanded="false"
aria-controls="c0204">
View Summary
</button>
</p>
<div class="collapse" id="c0204">
<div class="card card-body">
Thyroid follicular carcinomas frequently exhibit RAS mutation, and
closely resemble benign follicular adenomas with respect to
morphology
and differentiation. Cell culture studies suggest that at least one
requirement for progression from an adenoma to a carcinoma is
failure of
an intrinsic mechanism that normally limits the proliferative
lifespan
of RAS-induced cell clones. One current candidate for over-riding
the
mechanism is the tumor suppressor gene p16 INK4a.
<br><br>
There is great clinical interest in this area, as currently there is
no
marker to distinguish between thyroid follicular adenoma and
carcinoma
when evaluating fine needle aspirates and biopsies of thyroid
glands.
This means that many people have unnecessary operations on the basis
of
presumed malignancy. We now therefore wish to carry out a
comprehensive
comparison between thyroid carcinoma and adenoma cells to identify
differences that may confer an extended proliferative lifespan on
carcinoma cells.
</div>
</div>
</li>
<li>[003/2004] Molecular Definition of Gene Expression in Chernobyl Thyroid
Cancers
<div>
<span class="fw-light">Carine Maenhaut, ULB, Brussels</span>
<a href="mailto:cmaenhau@ulb.ac.be" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0304" aria-expanded="false"
aria-controls="c0304">
View Summary
</button>
</p>
<div class="collapse" id="c0304">
<div class="card card-body">
<p>
Chernobyl thyroid cancers represent a unique resource in
oncology
and radiation biology. They appear in a cohort of patients
irradiated at the same time and in which there is no doubt that
the
cancer originated from radiation exposure. The precise timing of
the
course allows to follow precisely the kinetics of appearance of
the
cancers. On the other hand study of the gene expression pattern
of
cancers by microarrays allows a precise molecular definition of
each
cancer. Using this methodology we were able to show that the
clustering of gene patterns of Chernobyl cancers of the first
wave
and European and US sporadic cases could not separate them. This
work should now be extended to a larger series of cases.
<ol>
<li>
to try to distinguish subtypes of Chernobyl and sporadic
papillary carcinomas and their signature.
</li>
<li>
to relate patterns of gene expression with clinical
variables
such as the duration of the incubation period and with the
genetic diagnosis.
</li>
<li>
to validate data at the RNA level by PCR and at the protein
level by Western and to define potential diagnostic markers
and
therapeutic targets.
</li>
</ol>
</p>
</div>
</div>
</li>
<li>[001/2005] Genomic Analysis of Gene Copy Number in Thyroid Cancer.
<div>
<span class="fw-light">PE Neiman, FHCRC, Seattle, USA</span>
<a href="mailto:pneiman@fhcrc.org" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0105" aria-expanded="false"
aria-controls="c0105">
View Summary
</button>
</p>
<div class="collapse" id="c0105">
<div class="card card-body">
<p>
High copy-number gene amplification is known to take place at a
few
genomic loci in numerous human cancers, but widespread low-level
copy-number changes in genomic DNA have not been described. cDNA
microarray-based comparative genome hybridization yields
high-resolution copy-number profiles that enable the detection
of
low-level amplification events at individual gene loci. We have
shown in a small pilot study that pediatric thyroid carcinoma in
residents of a region contaminated by 131I from the Chernobyl
accident (the Bryansk Oblast) exhibits gene amplification at a
higher frequency than that seen in pediatric thyroid carcinoma
in US
children with no history of radiation exposure. This result
suggests
that exposure to ionizing radiation from the environment may be
associated with an increased rate of gene amplification in a
human
cancer. The consistent amplification of many genes among cases
of
post-Chernobyl thyroid carcinoma from Bryansk suggests the
existence
of a target pool of radiation-sensitive genomic loci that
respond to
exposure by initiating local amplification events. The pattern
of
gene amplification may represent a radiation signature that
could be
used to map amplicons likely to harbor participating oncogenes.
<br><br>
Based upon these differences observed in the pilot study in
apparent
gene amplification between post-Chernobyl and spontaneous
pediatric
papillary thyroid carcinoma (PTC), we hypothesize that radiation
exposure leaves a measurable genomic signature in the form of
stable
changes in gene amplification. Some chromosomal regions
identified
by this method are likely to harbor participating oncogenes, but
it
is unreasonable to expect that so many genes be directly
involved in
oncogenesis. We hypothesize the presence of genomic hot spots in
human DNA that are susceptible to radiation-induced
amplification.
These genomic targets are unlikely to be saturated by the doses
of
radiation delivered to these patients. The number of targets hit
in
each case should therefore be directly proportional to radiation
dose.
</p>
</div>
</div>
</li>
<li>[002/2005] The influence of genetic variation in DNA repair pathways on
cancer
risk following exposure to ionising radiation.
<div>
<span class="fw-light">S Forbes-Robertson, Swansea Medical School, Swansea UK</span>
<a href="mailto:gerry.thomas@imperial.ac.uk" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0205" aria-expanded="false"
aria-controls="c0205">
View Summary
</button>
</p>
<div class="collapse" id="c0205">
<div class="card card-body">
<p>
Genetic damage following radiation exposure is subject to
correction
by the caretaker systems of DNA repair. Our interest is in the
role
that these systems may play in the molecular pathogenesis of
cancer.
We propose a pilot project to assess the influence of genetic
variation on cancer risk following exposure to ionising
radiation.
This will be achieved by investigation of variation in the genes
involved in the DNA repair pathways, in DNA derived from blood
samples or normal tissue samples from patients with thyroid
tumors
of radiation-associated and non-radiation-associated etiology.
There
are two main justifications for such a study, first to identify
SNPs
which indicate possession of an at risk genotype, and secondly,
to
identify the genes in which genetic variation is a significant
modulator of cancer risk. This has particular and wider
relevance to
the involvement of DNA repair-associated factors in the
pathology of
other cancers as well, such as breast cancer.
<br><br>
Genotyping of genes involved in double-strand break repair will
be
performed using a mass spectrometry-based SNPing platform which
has
been developed by our group at the University of Wales, Swansea.
Data will be provided to the Chernobyl Tissue Bank for
correlation
with pathology and expression of oncogenes such as ret and BRAF.
</p>
</div>
</div>
</li>
<li>[001/2007] Array CGH analysis of RET/PTC-positive and RET/PTC-negative
post-Chernobyl thyroid tumors.
<div>
<span class="fw-light">H Zitzelsberger, Helmholtz Zentrum München, Neuherberg, Germany</span>
<a href="mailto:zitzelsberger@helmholtz-muenchen.de" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0107" aria-expanded="false"
aria-controls="c0107">
View Summary
</button>
</p>
<div class="collapse" id="c0107">
<div class="card card-body">
<p>
It is proposed to study chromosomal imbalances in post-Chernobyl
papillary thyroid carcinomas (PTC) by means of array CGH using
1Mb
BAC arrays. As derived from interphase FISH experiments RET/PTC
rearrangements are heterogeneously distributed within tumor
tissues
leading to the assumption that additional gene alterations may
play
an important role in these tumors. To address this question
post-Chernobyl PTC, with and without RET/PTC rearrangements,
will be
analysed by array CGH. Altered candidate genes will be derived
from
recurrent regions of amplifications and deletions and will be
confirmed by interphase FISH on paraffin sections and further
studies by PCR-based approaches to investigate expression of
these
genes. In a first pilot study it is intended to compare 10
RET/PTC-positive (RET/PTC3) and 10 RET/PTC-negative cases with
similar histological features, a comparable age range of
patients at
time of exposure and a similar latency after exposure is a first
study. The pilot study will use cases from the age-matched
series
with known RET/PTC status. If successful this study will be
extended
to a larger series of cases linked to the GENRISK-T project.
</p>
</div>
</div>
</li>
<li>[002/2007] Expression profiling of childhood thyroid cancer: a comparison of
those exposed to radioiodine and those exposed to low level radiocaesium.
<div>
<span class="fw-light">Carine Maenhaut, University of Brussels School of Medicine, Brussels, Belgium</span>
<a href="mailto:cmaenhau@ulb.ac.be" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0207" aria-expanded="false"
aria-controls="c0207">
View Summary
</button>
</p>
<div class="collapse" id="c0207">
<div class="card card-body">
<p>
The aim of this study is to investigate whether different
transcriptomic profiles can be related to exposure to
radioiodine in
fallout from the Chernobyl accident and to lower level
radiocaesium
exposure present in the contaminated environment. We will use
Affymetrix microarray technology to define transcriptomic
profiles
in two cohorts of children, matched on age, oblast and
pathological
type of tumor. The research will be carried out in two separate
laboratories and cross-validated. This project is one of a
series of
projects that will study the transcriptomic and genetic profile
of
two well-defined cohorts to investigate the relative effects of
radioiodine and radiocaesium exposure on the development of
thyroid
cancer.
</p>
</div>
</div>
</li>
<li>[003/2007] Gene expression in normal and cancerous tissue in relation to
I-131
exposure.
<div>
<span class="fw-light">M Abend, Bundeswehr Institute of Radiobiology, Munich, Germany</span>
<a href="mailto:michaelabend@bundeswehr.org" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0307" aria-expanded="false"
aria-controls="c0307">
View Summary
</button>
</p>
<div class="collapse" id="c0307">
<div class="card card-body">
<p>
Gene expression has received less attention than the role of
germline polymorphisms or somatic mutations in studies of
radiation
and thyroid cancer. The increase in papillary thyroid cancers
(PTC)
in exposed children following the Chernobyl nuclear accident
presents an opportunity to pursue the role of gene expression
further. Recently, we reported on expression of seven genes,
each of
which was able to distinguish post-Chernobyl PTCs from sporadic
PTCs
(Port et al 2007). Our approach involved (i) a whole genome
microarray used for screening purposes; and (ii) quantitative
examination of the 92 target genes with a high throughput
RTQ-PCR
technique (LDA). The study had some limitations such as the
origin
of sporadic PTCs (Eastern Germany), their different age at
diagnosis
and a small number of cases (n=11). Subsequently another group
has
reported on expression of thirteen genes involved in homologous
recombination suggesting a distinct radiation pattern of
post-Chernobyl PTCs (Detours et al 2007). Using the already
established 2-stage design, the purpose of the present
application
is to overcome limitations in the previous study and extend the
findings (Port et al 1007) by evaluating a dose-dependent gene
expression pattern in 74 post-Chernobyl PTCs with individual
I-131
dose estimates.
</p>
</div>
</div>
</li>
<li>[004/2007] Genetic predisposition to radiation-induced carcinogenesis and to
specific genetic alterations in post-Chernobyl thyroid cancer.
<div>
<span class="fw-light">Y Nikiforov, University of Pittsburgh School of Medicine, Pittsburgh, USA</span>
<a href="mailto:nikiforovye@upmc.edu" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0407" aria-expanded="false"
aria-controls="c0407">
View Summary
</button>
</p>
<div class="collapse" id="c0407">
<div class="card card-body">
<p>
Radiation exposure is a well established risk factor for thyroid
cancer. Ionising radiation is known to cause extensive DNA
damage
including double strand breaks, which may lead to the generation
of
somatic mutations in thyroid cells and cancer initiation.
However,
environmental triggers cannot fully explain the inter-patient
heterogeneity in the individual response to exposure to
radiation,
which points to the existence of genetic variations that define
the
individual susceptibility to radiation-related cancer. We
propose to
analyse several candidate DNA repair genes and perform a
genome-wide
analysis of single nucleotide polymorphisms (SNPs) in Ukrainian
patients who developed thyroid cancer after Chernobyl and in
control
cancer-free individuals to identify mutations and SNPs that are
involved in genetic predisposition and to identify the genes
that
are affected. We will then perform functional analysis to find
whether these genetic variations alter gene function. We will
also
study the link between specific SNPs and known or new mutations
found in these tumors. The overall goal of this study is to
identify
genes involved in genetic predisposition to radiation-associated
thyroid carcinogenesis and a pattern of SNPs that can detect it.
</p>
</div>
</div>
</li>
<li>[001/2008] Genrisk-T - defining the risk of low dose radiation for thyroid
cancer - the role of germline SNPs.
<div>
<span class="fw-light">GA Thomas, Imperial College London, Hammersmith Hospital, London</span>
<a href="mailto:gerry.thomas@imperial.ac.uk" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0108" aria-expanded="false"
aria-controls="c0108">
View Summary
</button>
</p>
<div class="collapse" id="c0108">
<div class="card card-body">
<p>
Cancer of the non-medullary (follicular epithelium) component of
the
thyroid is induced by external irradiation and by radionuclides
deposited within the thyroid tissue. Estimates of the
radiological
risk of developing thyroid cancer are derived from
epidemiological
studies performed in. Populations receiving high doses where,
according to Ron et al, the threshold in 100 mSv. Extrapolation
of
this risk to exposures at much lower doses is compromised by the
lack of an accurate model of the dose response curve for thyroid
cancer at low doses. Moreover, such population based estimates
fail
to take into account the contribution of individual genetic
variability to the risk estimate. Individuals with an increased
genetic predisposition to develop thyroid cancer are not
identified,
and it is precisely these individuals who will be at greatest
risk
at low doses. The GENRISK-T consortium is composed of thyroid
cancer
experts with experience in the fields of radiation biology,
animal
models of radiation-induced cancer, tumor banking, cancer
biology,
molecular genetics, histopathology, cyto genetics and risk
modelling. We will use this interdisciplinary knowledge to
define
the genetic component influencing the risk of radiation-induced
thyroid cancer. This will be achieved through a combination of
studies using animal models and in human radiation-induced
thyroid
tumors. This new understanding of the genetic risk modifiers
will be
used to develop an animal model of thyroid cancer that is
responsive
to low dose radiation in the cGy range, thereby providing an
experimental solution to resolving the uncertainties of the low
dose-response curve. This EC collaborative project (PI Professor
M
Atkinson, Helmholtz Zentrum, Munich) combines the use of animal
models and human studies. This particular application is to
support
the investigation of human germline SNPs that may predispose to
radioiodine induced thyroid cancer in those exposed as children
and
adolescents.
</p>
</div>
</div>
</li>
<li>[002/2008] Expression profiling of childhood follicular tumors: a comparison
of
those exposed and not exposed to radiation. Defining the genetic component
of
thyroid cancer risk at low doses.
<div>
<span class="fw-light">B Jarzab, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice, Poland</span>
<a href="mailto:bjarzab@io.gliwice.pl" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0208" aria-expanded="false"
aria-controls="c0208">
View Summary
</button>
</p>
<div class="collapse" id="c0208">
<div class="card card-body">
<p>
The aim of the study is to investigate transcriptomic profiles
of
follicular thyroid tumors (malignant and benign) that arose
after
expose to radioiodine fallout from Chernobyl power station and
to
low level radiocesium exposure present in the contaminated
environment. Affimetrix microarray technology will be employed
to
define transcriptomic profiles in two cohorts of children
matched on
age, oblast and pathological type of tumor. This project is the
continuation of a series of projects that are carry on to
investigate the transcriptomic and genetic profile of radiation
induced thyroid cancer.
</p>
</div>
</div>
</li>
<li>[003/2008] Array CGH analysis of follicular post-Chernobyl thyroid tumors.
<div>
<span class="fw-light">H Zitzelsberger, Helmholtz Zentrum Muenchen, Neuherberg Germany</span>
<a href="mailto:zitzelsberger@helmholtz-muenchen.de" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0308" aria-expanded="false"
aria-controls="c0308">
View Summary
</button>
</p>
<div class="collapse" id="c0308">
<div class="card card-body">
<p>
Follicular thyroid cancers are less frequent than papillary
thyroid
carcinomas (PTC), however, they are associated with a poorer
survival outcome than PTC. Although several genetic changes have
been identified so far, the molecular genetic mechanisms of
tumor
development in follicular thyroid neoplasms are still unclear.
<br><br>
To investigate novel gene alterations and potential radiation
signatures in follicular thyroid adenomas (FA) and follicular
thyroid carcinomas (FTC) it is proposed to investigate
genome-wide
copy number changes of 100 thyroid tissue samples by array CGH
using
1 Mb BAC arrays. For this purpose we want to compare genomic
profiles of tumors (FA and FTC) developed pre- and post-fallout
of
the Chernobyl accident. The proposed study aims to identify gene
alterations in follicular thyroid neoplasms from altered genomic
regions and to determine aberrations patterns that correlate
with
the radiation history of patients as well as with any of the
clinical phenotypes of the tumors.
</p>
</div>
</div>
</li>
<li>[001/2009] Defining the genetic component of thyroid cancer risk at low
doses
request for RNA aliquots for QPCR validation and for the exon arrays.
<span class="fw-light fst-italic">(This project is an expansion of project 002/2008)</span>
<div>
<span class="fw-light">B Jarzab, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice, Poland</span>
<a href="mailto:bjarzab@io.gliwice.pl" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0109" aria-expanded="false"
aria-controls="c0109">
View Summary
</button>
</p>
<div class="collapse" id="c0109">
<div class="card card-body">
<p>
The aim of the study is to seek for differences in
transcriptomic
profiles of childhood papillary thyroid cancers that arose after
radiation exposure from Chernobyl power station fallout and
sporadic
cancers. As the first step Affimetrix microarray technology was
employed to define transcriptomic profiles in two cohorts of
children matched on age, oblast and pathological type of tumor.
The
second step of the study is to validate microarray results with
Q-PCR analysis. We also plan to extent the analysis to exon
microarray study which allow to detect transcript isoforms,
chromosomal deletions and amplifications.
</p>
</div>
</div>
</li>
<li>[002/2009] Identification of somatically acquired rearrangements in
post-Chernobyl paediatric thyroid cancers using genome-wide massively
parallel
paired-end sequencing
<div>
<span class="fw-light">JA Fagin, Memorial Sloan-Kettering Cancer Center, New York, USA</span>
<a href="mailto:faginj@mskcc.org" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0209" aria-expanded="false"
aria-controls="c0209">
View Summary
</button>
</p>
<div class="collapse" id="c0209">
<div class="card card-body">
<p>
Post-Chernobyl pediatric thyroid cancers are associated with a
high
frequency of recombination events leading to the generation of
fusion oncogenes, resulting in aberrant expression and
activation of
RET, and less frequently of NTRK and BRAF. Altogether, ~60% of
PTC
arising in this patient population harbor one of these
abnormalities. The discovery of novel somatic rearrangements
using
conventional methods has low sensitivity and/or resolution. We
propose to use genome-wide parallel paired-end sequencing to
identify somatic rearrangements in childhood thyroid cancers
induced
by radiation, as compared to age-matched thyroid cancers without
radiation exposure. Altogether we will select 6 samples of each
population: 2 with a known rearrangement in RET, NTRK or BRAF
(as
positive controls), and 4 without. We will construct 3kb insert
Illumina libraries from each tumor DNA sample, and ~35bp of
sequence
from both ends of each fragment will be obtained. Each end will
be
mapped back to the reference genome. Fragments for which the
ends do
not map back within 3kb of each other and/or are in
inappropriate
orientation will be further studied as they may represent
rearrangements present in the thyroid cancer genome. We will
acquire
~1 fold genome coverage (~3Gb) from each sample. This will
approximate to 30-fold physical coverage, allowing detection of
essentially all rearrangements present in the dominant clone of
the
cancer. Rearrangements will be processed using a suite of
informatics tools to predict which may generate an in-frame
fusion
gene. RNA from each of the samples will then be tested by
exon-exon
PCR to determine whether the fusion is expressed, and based on
its
predicted function, whether it may correspond to a driver
mutation.
The number of rearrangements in each cancer and their
architecture
will then be compared between the two classes. Sequences at the
rearrangement junctions will also be compared particularly to
examine the complexity of the rearrangement, sequence contexts
of
breaks, presence of repeats and overlapping microhomology of the
rearrangement. Each of these indices may provide clues to the
way
large radiation doses induce DNA double strand breaks and how
they
are repaired.
</p>
</div>
</div>
</li>
<li>[003/2009] miRNA profiles in childhood thyroid cancer
<div>
<span class="fw-light">GA Thomas, Imperial College London, Hammersmith Hospital, London</span>
<a href="mailto:gerry.thomas@imperial.ac.uk" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0309" aria-expanded="false"
aria-controls="c0309">
View Summary
</button>
</p>
<div class="collapse" id="c0309">
<div class="card card-body">
<p>
MicroRNAs (miRNAs) are 21-23 nucleotide long non-coding RNA
molecules that have been shown to regulate the stability or
translational efficiency of target messenger RNAs. Dysregulation
of
miRNAs has been implicated in a variety of cancers, and in the
thyroid germline SNPs in miRNA binding sites and in the coding
sequence for miRNAs themselves, have been implicated in
Papillary
Thyroid carcinogenesis. The Human Cancer Studies Group is part
of an
EC sponsored consortium (Genrisk-T) that has intensively studied
papillary carcinomas from a series of 100 patients, and is
currently
extending this approach to follicular tumors. Half of this group
were exposed to radiation and half were born after 1/1/87 and
not
exposed to radioiodine in fallout. The cohort is carefully age
and
sex matched. The Genrisk-T project has provided data on RNA
expression using Affymetrix technology, bac array CGH data on
copy
number variation in the tumors and SNP array data from normal
tissue
from these patients. We now seek to add miRNA data from this
cohort
and to correlate data on SNPs and copy number variation in the
tumor, with changes in miRNA level, and miRNA expression levels
with
changes in RNA expression levels. The combination of this data
will
give us a thorough understanding of the regulation of a number
of
different growth control pathways involved in carcinogenesis of
the
thyroid follicular cell and their relationship to radiation
exposure.
</p>
</div>
</div>
</li>
<li>[002/2007-1] Validation of statistical and bioinformatics technologies to
allow
integration of Next generation RNA Sequencing and microarray data.
<div>
<span class="fw-light">L van Zyl, ArrayXpress, Inc. Raleigh, North Carolina, USA</span>
<a href="mailto:lenvanzyl@arrayxpress.com" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0207-1" aria-expanded="false"
aria-controls="c0207-1">
View Summary
</button>
</p>
<div class="collapse" id="c0207-1">
<div class="card card-body">
<p>
We are a small biotech company developing statistical and
bioinformatics methodology that would allow for the direct
integration and co-analyses of RNA-seq and microarray data. As
quantitative RNA-seq data is becoming the method of choice for
gene
expression analyses, we are developing the statistical and
bioinformatics technology which that allow all previous
published
microarray data to be incorporated with new gene expression
platform
data, to ultimately provide more comprehensive data-sets for
downstream applications/analyses.
<br><br>
We have been working with Dr C Maenhauts group to develop the
methodology to integrate her published Affymetrix gene
expression
data with our own Illumina RNA-seq data from papillary thyroid
cancers. We propose now to subject surplus material from the
samples
that Dr Maenhaut received from the CTB (project 002/2007) to
RNA-seq
in order to not only obtain additional expression data over and
above that obtained by microarray but also to further validate
our
methodologies.
</p>
</div>
</div>
</li>
</ul>
<a href="#"><i class="fas fa-arrow-up"></i> Go to top</a>
</div>
</div>
</div>
<div class="accordion-item">
<h2 class="accordion-header">
<button class="accordion-button collapsed" type="button" data-bs-toggle="collapse"
data-bs-target="#flush-collapseTwo" aria-expanded="false"
aria-controls="flush-collapseTwo">
Research Projects: 2010-2019
</button>
</h2>
<div id="flush-collapseTwo" class="accordion-collapse collapse"
data-bs-parent="#accordionFlushResearch">
<div class="accordion-body">
<ul>
<li>[001/2011] EpiRadiBio
<div><span
class="fw-light">K Unger, Helmholtz Centre, Munich, Germany</span>
<a class="ms-2"
href="mailto:unger@helmholtz-muenchen.de"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0111" aria-expanded="false"
aria-controls="c0111">
View Summary
</button>
</p>
<div class="collapse" id="c0111">
<div class="card card-body">
<p>The EU funded project EpiRadBio project seeks to model the cancer
of the lung, breast and the thyroid after exposure to radiation
in the low-dose range (cumulative dose < 100 mGy). The
formalin-fixed paraffin-embedded (FFPE) papillary thyroid cancer
tissue sections we apply for will be used in a work package of
EpiRadBio that focuses on the cancer risk of papillary thyroid
cancer. In another, recently finished EU funded project on young
onset childhood thyroid carcinomas that also used CTB material
we found that a gain of the chromosome band 7q11 was associated
with exposure to low-dose ionising radiation (He et al., PNAS,
in press). The FFPE tumor sections from patients, which are part
of the UkrAm cohort and which come with estimates on radiation
dose the patients have received will be used for validation and
further characterisation of this marker. The FFPE sections will
be used for in situ hybridisation (FISH) using 7q11 specific
probes. DNA and total RNA will also be extracted from the FFPE
sections. The DNA will be used for high-resolution array CGH and
the total RNA for qRT-PCR mRNA expression analysis of candidate
genes from the gained region. The copy number data and qRT-PCR
data will be integrated with the dose estimates in order to
identify a potential relationship between the
radiation-associated biomarker and radiation dose. The resulting
data will be provided to the modellers of the project who will
use this information to build and refine their models on
radiation risk of papillary thyroid cancer after exposure to
low-dose ionising radiation.</p>
</div>
</div>
</li>
<li>[002/2011] Molecular specificities of radiation-induced thyroid tumors.
<div>
<span class="fw-light">C Ory, Commissariat Energie Atomique, Departement Sciences du vivant, Institut de radiobiologie cellulaire et moleculaire, Laboratoire de Cancerologie Experimentale (CEA), France
UK.</span> <a href="mailto:catherine.ory@cea.fr" class="ms-2"><i class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0211" aria-expanded="false"
aria-controls="c0211">
View Summary
</button>
</p>
<div class="collapse" id="c0211">
<div class="card card-body">
The constituted network to realise this program involved two teams
well known in diagnosis and treatment of thyroid tumors and one team
which were already implicated in the search of radiation-induced
signatures in the thyroid and in the identification of the molecular
mechanisms of radiation-induced tumorigenesis. To date, we focused
our approach at the transcriptomic level. We wish now to analyse
miRNA and mRNA deregulations in a series of post-Chernobyl thyroid
tumors by microarray analysis: 1) to identify a radiation-induced
miRNA and mRNA signatures. We will assess the robustness of these
signatures for a potential use as a diagnostic tool alone or in
combination. 2) to obtain an integrated miRNA/mRNA overview of
radiation-induced tumorigenesis by taking advantage of the
deregulated pathway identified by the transcriptomic approach. To
date, no such integrated analysis has been performed as most of the
studies focused on either transcriptome analysis or miRNA analysis
separately. Ultimately, we will cross the obtained data with others
results from analysis of post-radiotherapy tumors (Ory et al. 2011;
Ugolin et al. PLosONE under revision).
</div>
</div>
</li>
<li>[003/2011] EpiRadBio - Validation of radiation-associated gain of chromosome
band 7q11.
<div>
<span class="fw-light">K Unger, Helmholtz Centre, Munich, Germany</span>
<a href="mailto:unger@helmholtz-muenchen.de" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0311" aria-expanded="false"
aria-controls="c0311">
View Summary
</button>
</p>
<div class="collapse" id="c0311">
<div class="card card-body">
The project using the applied biomaterial is an extension of the
EU-funded GENRISK-T project and aims to validate a gain on
chromosome band 7q11 that was found to be associated with papillary
thyroid carcinomas from young patients (< 19 years) that were
exposed to radiation from the Chernobyl fallout at very young age
(median: 2 years). The validation set containing exposed and
unexposed cases will be matched for age, morphology and residence -
these criteria were already used for case selection of the GENRISK-T
set. A high-definition array CGH platform will be used to validate
the gain and to type for additional radiation-markers that are
smaller in size and were therefore not detectable by 1Mb BAC array
CGH that was used in GENRISK-T. Further, we will use RNA samples and
paraffin sections for characterisation of expression candidate genes
and proteins by qRT-PCR and immunohistochemistry. Fresh-frozen
tissue from selected samples expressing the candidate gene CLIP2
from the gained region on 7q11 and those that do not express the
gene will be analysed using a whole proteomics approach (liquid
chromatography-tandem mass spectrometry, LC-MS/MS). The results will
be used to identify the dysregulation networks in which CLIP2 is
specifically involved. The projects aims to validate the radiation
marker on chromosome band 7q11, to identify the networks that are
dysregulated in tumors harbouring the marker and to find new markers
that are associated with exposure to radiation.
</div>
</div>
</li>
<li>[004/2011] A Sequence-based Approach to Identify Genetic Determinants of
Tumorigenesis in Radiation-Induced Pediatric Papillary Thyroid Carcinomas.
<div>
<span class="fw-light">L Hawthorn, Georgia Health Sciences University, USA</span>
<a
href="mailto:lhawthorn@georgiahealth.edu" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0411" aria-expanded="false"
aria-controls="c0411">
View Summary
</button>
</p>
<div class="collapse" id="c0411">
<div class="card card-body">
<p>
Cancer is a genetic disease, a concept which has been
consistently
observed for all tumors. Our approach is to survey the entire
genome
of these tumors to look for mutations and other perturbations
that
are involved in radiation-induced papillary thyroid carcinoma
(RI-PTC) and create a genomic profile of this tumor. A new
technology, termed Next-generation sequencing allows sequencing
of
the entire human genome in 8 days. We will begin by sequencing
the
DNA of 50 individual RI-PTC tumors from Chernobyl pediatric
patients
to look for mutations in genes. We will correlate this data with
RNA
sequencing from the same patient samples. This data will provide
information about events that are taking place at the level of
gene
expression, providing information about over and under expressed
genes and the expression of aberrant genes, and gene fusion
products. This data will be compared to RIP-PTC in age matched
patients who were not exposed to radiation to develop a
radiation-specific profile. We have bioinformatic specialists in
the
group who will integrate these various kinds of data. This study
will provide a comprehensive profile of RIP-PTC.</p>
</div>
</div>
</li>
<li>[001/2012] EpiRadBio integrative analysis of molecular data.
<div>
<span class="fw-light">W van Wieringen, VU University Medical Centre, Amsterdam, The Netherlands</span>
<a
href="mailto:w.vanwieringen@vumc.nl" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0112" aria-expanded="false"
aria-controls="c0112">
View Summary
</button>
</p>
<div class="collapse" id="c0112">
<div class="card card-body">
<p>Within the scope of the EpiRadBio-project, Mark van de Wiel,
Carel Peeters and Wessel van Wieringen from the department of
Epidemiology & Biostatistics of the VU University Medical Center
are responsible for integrative analysis of the molecular data
from (radiation) exposed and non-exposed thyroid cancer samples.
Integrative analysis combines heterogeneous biological data, be
it experimental (e.g., copy number, gene expression, microRNA
expression) or from the biological literature (e.g., gene
annotation, pathway information). Integration of data from
multiple sources is imperative for a mechanistic understanding
of cancer. By putting together partial views of a complex
process like tumorgenesis, we may obtain a more accurate and
complete picture of the molecular mechanisms underlying it. No
off-the-shelf methodology for the statistical analysis of the
data is available. We therefore aim to develop statistical
models from the experimental data of these biological processes.
Such models will enhance our ability to identify biomarkers and
therapeutic targets more unambiguously and to interpret genotype
information. This should enhance the understanding of what
distinguishes the exposed from the non-exposed thyroid cancers.
In addition, the biological insight these models provide is
likely to result in more targeted follow-up experiments and
efficient use of available resources.</p>
</div>
</div>
</li>
<li>[002/2012] Validation of the gene signature differentiating exposed from
non-exposed PTCs, obtained in the Genrisk-T project (no.: 036495) with an
independent QPCR method.
<div>
<span class="fw-light">B Jarzab, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice, Poland</span>
<a
href="mailto:bjarzab@io.gliwice.pl" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0102" aria-expanded="false"
aria-controls="c0102">
View Summary
</button>
</p>
<div class="collapse" id="c0102">
<div class="card card-body">
<p>The aim of the study is to investigate transcriptomic profiles of
papillary thyroid carcinomas that arose after expose to
radioiodine fallout from Chernobyl power station and to low
level radiocesium exposure present in the contaminated
environment. This project is the continuation of a series of
projects that are carry on to investigate the transcriptomic and
genetic profile of radiation induced thyroid cancer.
As a first step of the study Affimetrix microarray technology
was employed to define transcriptomic profiles in two cohorts of
children matched on age, oblast and pathological type of tumor.
At present we want to validate the results with qPCR.</p>
</div>
</div>
</li>
<li>[001/2013] A detailed study of the somatic genomics of radiation induced
thyroid cancer.
<div>
<span class="fw-light">GA Thomas, Imperial College, London</span>
<a href="mailto:geraldine.thomas@imperial.ac.uk" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0113" aria-expanded="false"
aria-controls="c0113">
View Summary
</button>
</p>
<div class="collapse" id="c0113">
<div class="card card-body">
<p>
It has long been accepted that cancers arise by the sequential
accumulation of errors in the DNA of a clone of cells within a
given tissue. This in part explains their long latency. However,
recent studies using whole genome sequencing have suggested a
different mechanism for some cancers, particularly those that
arise in children. This mechanism is called chromothripsis and
involves shattering of chromosomes and then restitching them
together. This results in multiple small changes in the DNA that
occur simultaneously rather than sequentially. The aim of this
study is to use whole genome sequencing to identify novel
mutations in radiation induced thyroid cancer, to identify
changes in the mitochondrial genome and to investigate the
frequency of chromothripsis in childhood thyroid cancer,
especially with respect to radiation exposure.</p>
</div>
</div>
</li>
<li>[001/2014] Assessing the impact of radiation exposure on the development of
medullary thyroid carcinoma.
<div>
<span class="fw-light">Elizabeth Grubbs, Department Surgical Oncology, MD Anderson Cancer Center, Houston, USA</span>
<a href="mailto:eggrubbs@mdanderson.org" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0114" aria-expanded="false"
aria-controls="c0114">
View Summary
</button>
</p>
<div class="collapse" id="c0114">
<div class="card card-body">
<p>Convincing epidemiologic data has established a strong causative
association between ionizing radiation and the development of
papillary thyroid cancer (PTC). This finding was due, in large
part, to studying those affected by the Chernobyl accident. More
recently other solid tumors, such as lung and breast, have been
associated with radiation. Medullary thyroid cancer (MTC), a
rarer but more lethal thyroid cancer than PTC, has not been
associated with radiation exposure to date. However, there
appears to be a higher number of MTC cases than would be
expected in the Chernobyl population. We would like to determine
if there is a link between radiation and MTC by studying this
population to look for mutations that are associated with
radiation exposure. Additionally, because MTC is a hereditary
condition in 25% of cases, we would also like to assess whether
there could be a hereditary cause to MTC in this small
geographic region. Such data will give us an insight into the
mechanisms in which tumors are formed in MTC and potentially
help us target ways to stop these tumors.</p>
</div>
</div>
</li>
<li>[002/2014] Anaplastic lymphoma kinase (ALK) rearrangements in
radiation-induced papillary thyroid carcinomas: a study on post Chernobyl
tissue samples
<div>
<span class="fw-light">S Eder, Bundeswehr Institute of Radiobiology, Munich Germany</span>
<a href="mailto:stefanfriedricheder@bundeswehr.org" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0203" aria-expanded="false"
aria-controls="c0203">
View Summary
</button>
</p>
<div class="collapse" id="c0203">
<div class="card card-body">
<p>Previous analysis of data derived from the Chernobyl accident has
shown strong correlation between absorbed doses of IR and the
induction of papillary thyroid cancer (PTC). Specific genetic
alterations, such as rearrangements of the RET oncogene, are
linked to previous exposure to radioiodine. Recently,
rearrangements of the anaplastic lymphoma kinase (ALK) gene have
been found to be selectively expressed in papillary thyroid
cancer (PTC) amongst atomic bomb survivors (ABS), but not in PTC
patients lacking radiation exposure. In PTC, ALK rearrangements
have been shown to be associated with tumor aggressiveness and,
importantly, represent a possible pharmacologicaltarget for the
compound Crizotinib. Interestingly, radiation-induced PTCs that
show ALK rearrangements lack additional genetic alterations that
are frequently found in sporadic thyroid cancer, such as RET,
NTRK1, BRAF, or RAS; these findings underline the oncogenic
potential of ALK rearrangements in radiation-induced PTC. We
plan to investigate a possible correlation between radiation
exposure and ALK rearrangements in PTC biospecimens from
patients exposed to radioiodine in the context of the Chernobyl
accident as well as in a control cohort of sporadic PTCs,
performing fluorescence in situ hybridization (FISH) analyses.
Furthermore, we intend to assess the mutation status of commonly
altered oncogenes in PTC, such as BRAF or RAS, using
pyrosequencing.</p>
</div>
</div>
</li>
<li>[003/2014] Comprehensive Genomic Characterization of Radiation-Related
Thyroid Cancer in Ukraine
<div>
<span class="fw-light">S Channock, Division of Cancer Epidemiology and Genetics, National Cancer Institute, USA</span>
<a href="mailto:chanocks@mail.nih.gov" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0314" aria-expanded="false"
aria-controls="c0314">
View Summary
</button>
</p>
<div class="collapse" id="c0314">
<div class="card card-body">
<p>New advances in genomic characterization technologies afford new
opportunities to comprehensively investigate the genetic basis
of the established association between childhood exposure to
iodine-131 (I-131) from the Chernobyl Nuclear Power Plant
accident and risk of thyroid cancer. The opportunity to analyze
a large set of thyroid cancers and normal tissue/blood from the
Chernobyl Tissue Bank (CTB) could further our understanding of
the molecular mechanisms of radiation carcinogenesis in humans
based on careful evaluation of epidemiological risk factors and
genomic alterations. Previously, we had reported a preliminary
study of dose-related alterations in gene expression and
chromosomal translocations in approximately 70 cases drawn from
the Ukrainian-American (UkrAm) cohort component of the CTB
biorepository. Recently, we have completed a pilot study in
which we have conducted a comprehensive genomic characterization
of 12 UkrAm cases, including paired fresh frozen and
formalin-fixed paraffin-embedded tissue samples using the
infrastructure and analytical pipeline of the Cancer Genome
Atlas (TCGA) of the U.S.A. National Cancer Institute (NCI). This
includes whole genome sequence analysis of RNA, DNA and
micro-RNAs as well SNP and methylation microarrays of the tumor
tissue. SNP microarray and DNA analysis was performed on
peripheral blood for comparison of germline to somatic
alterations. The success of the feasibility study establishes a
strong scientific basis for extending this approach to a
substantially larger study of thyroid cancer cases drawn from
the CTB. Here, we propose conducting a comprehensive genomic
characterization study of 500 papillary thyroid cancers (PTC)
from the Ukraine using biological samples, information on
radiation exposure, and demographic characteristics. The main
objective of the study is to provide comprehensive, integrated
characterization of the genomic, transcriptomic, and epigenomic
landscapes of radiation-related PTC for comparison across a
spectrum of I-131 exposure as well as a comparison with
approximately 500 sporadic PTCs available from The Cancer Genome
Atlas recently published in Cell. The proposed study has the
potential to provide unique insights into the mechanisms of
radiation carcinogenesis and to generate a rich data resource
accessible to other investigators.</p>
</div>
</div>
</li>
<li>[001/2018] Liquid biopsy in assessment of radio-induced thyroid cancer in
children and young adults
<div>
<span class="fw-light">Kirk Jensen, Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA</span>
<a href="mailto:kirk.jensen@usuhs.edu" class="ms-2"><i
class="far fa-envelope"></i> Email</a>
</div>
<p class="d-inline-flex gap-1">
<button class="btn btn-outline-secondary" type="button"
data-bs-toggle="collapse"
data-bs-target="#c0118" aria-expanded="false"
aria-controls="c0118">
View Summary
</button>
</p>
<div class="collapse" id="c0118">
<div class="card card-body">
<p>In this study we plan to analyze samples from patients with
papillary thyroid cancer. We will examine primary tumors and
serum samples in 40 pediatric patients (aged ≤ 18 years in
1986), and in 40 young adults (18-25 years in 1986). To
determine a possible correlation between the presence of
mutations/fusion in liquid biopsy and the extent of metastatic
spread we plan to examine samples from patients presenting with
lymph node metastases only and from patients with distant
metastases.</p>
<p>
We will first identify driver mutations in the primary tumor by
performing Ion Torrent Oncomine Pan-Cancer assay analysis using
DNA/RNA extracted from tumor. Next, we will employ the same
approach for analysis of DNA/RNA extracted from the serum sample
of the same patient. We expect to show that in patients with
metastatic thyroid cancers, results of NGS analysis in serum
will recapitulate results of NGS analysis in primary tumors. We
also plan to perform quantitative assessment of genomic
abnormalities using the digital PCR technique. To do so, we will
examine the presence of specific driver mutation(s) in primary
tumor by dPCR, and determine the mutant/wild copy numbers in
DNA/RNA samples extracted from the whole tumor. We also plan to
complete the assessment of primary tumors through the detection
of oncogenic proteins by immunohistochemistry, and by evaluation
of mutant/wild copy numbers after performing laser captured
microdissection. Serum from the same patient will be then
examined by dPCR.</p>
</div>
</div>
</li>
</ul>
<a href="#"><i class="fas fa-arrow-up"></i> Go to top</a>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
</main>
<footer class="mt-auto">
<div class="container-lg">
<div class="px-md-2 py-3 my-1">
<div class="row">
<div class="col-md-4 col-12 mb-4">
<h3 class="">Chernobyl Tissue Bank</h3>
<div class="fs-6">at the National Cancer Institute</div>
</div>
<div class="col-md-4 col-12 text-md-end mb-4">
<h4>Policies</h4>
<div class=""><a href="https://www.cancer.gov/policies/accessibility" target="_blank"
rel="noopener noreferrer">Accessibility</a></div>
<div class=""><a href="https://www.cancer.gov/policies/foia" target="_blank"
rel="noopener noreferrer">FOIA</a></div>
<div class=""><a href="/privacy/">Privacy Policy</a></div>
<div class=""><a href="https://www.hhs.gov/vulnerability-disclosure-policy/index.html"
target="_blank" rel="noopener noreferrer">HHS Vulnerability Disclosure</a></div>
</div>
<div class="col-md-4 col-12 text-md-end">
<h4>Contact Us
</h4>
<div>
<a href="mailto:ncicontactdceg@mail.nih.gov">For CTB Questions<i class="fas fa-envelope ms-2"></i></a>
</div>
<div>
<a href="mailto:ctbWebAdmin@mail.nih.gov">Help Desk<i class="fas fa-envelope ms-2"></i></a>
</div>
<div>
<a target="_blank" rel="noopener noreferrer" href="https://dceg.cancer.gov/about/contact-dceg">Contact
DCEG<i class="fas fa-globe ms-2"></i></a>
</div>
</div>
</div>
<div class="row mt-3" style="font-size: .9rem;">
<div class="col text-md-end">
<div>
<a target="_blank" rel="noopener noreferrer" href="https://www.hhs.gov/">U.S. Department of
Health and Human Services
</a>
</div>
<div>
<a target="_blank" rel="noopener noreferrer" href="https://www.nih.gov/">National Institutes of
Health
</a>
</div>
<div>
<a target="_blank" rel="noopener noreferrer" href="https://www.cancer.gov/">National Cancer
Institute </a>
</div>
<div>
<a target="_blank" rel="noopener noreferrer" href="https://usa.gov/">USA.gov</a>
</div>
<div class="mt-3">
<a target="_blank" rel="noopener noreferrer"
href="https://dceg.cancer.gov/research/what-we-study/chernobyl-nuclear-accident">Learn about
DCEG research on the Chernobyl accident <i class="fas fa-external-link-alt"></i></a>
</div>
<div class="mt-4"><a class="fs-5" href="#">Back to Top <i class="fas fa-arrow-circle-up"></i></a></div>
</div>
</div>
</div>
</div>
</footer>
<!-- Warning Modal -->
<div class="modal fade" id="gov_warning" tabindex="-1" role="dialog" data-backdrop="static"
aria-labelledby="gov_warning-header" aria-hidden="true">
<div class="modal-dialog">
<div class="modal-content">
<div class="modal-header">
<h4 class="modal-title" id="gov_warning-header">Warning</h4>
</div>
<div class="modal-body">
<p>You are accessing a US Government web site which may contain information that must be protected under
the
US Privacy Act or other sensitive information and is intended for Government authorized use
only. </p>
<p>Unauthorized attempts to upload information, change information, or use of this web site may result
in
disciplinary action, civil, and/or criminal penalties. Unauthorized users of this website should
have no
expectation of privacy regarding any communications or data processed by this website.</p>
<p> Anyone accessing this website expressly consents to monitoring of their actions and all
communications
or data transiting or stored on related to this website and is advised that if such monitoring
reveals
possible evidence of criminal activity, NIH may provide that evidence to law enforcement
officials</p>
</div>
<div class="modal-footer">
<button type="button" class="btn btn-primary" data-bs-dismiss="modal">OK</button>
</div>
</div>
</div>
</div>
<!-- Logout Modal -->
<div id="logout-modal" class="modal" tabindex="-1" role="dialog" aria-labelledby="logoutModalTitle" aria-hidden="true">
<div class="modal-dialog">
<div class="modal-content">
<div class="modal-header">
<h4 id="logoutModalTitle" class="modal-title">Logout</h4>
<button type="button" class="btn-close" data-bs-dismiss="modal" aria-label="Close"></button>
</div>
<form method="post" action="/accounts/logout">
<div class="modal-body">
<p>Are you sure you want to sign out?</p>
</div>
<div class="modal-footer">
<button type="button" class="btn btn-secondary" data-bs-dismiss="modal">Cancel</button>
<input type="hidden" name="csrfmiddlewaretoken" value="FearZS3YHxPLpIV5Co9D6LuuQuWG84BKMhMp2Y6A1fgipS5Ly973nKELXpz5xSyB">
<button type="submit" class="btn btn-primary">Sign Out</button>
</div>
</form>
</div>
</div>
</div>
<script>
var warningSeen = false;
var user_is_auth = false;
</script>
<!-- Additional includes brought in by specific child templates -->
<script type="text/javascript" src="/static/js/lib/require.js"></script>
<script type="text/javascript" src="/static/js/base.js?v=local-dev.202502242337"></script>
</body>
</html>
Reference in a new issue View git blame Copy permalink