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Comment
. 2012 Mar 20;21(3):325-6.
doi: 10.1016/j.ccr.2012.03.004.

ALK and MYCN: when two oncogenes are better than one

Zhihui Liu  1 , Carol J Thiele
Affiliations
Comment

ALK and MYCN: when two oncogenes are better than one

Zhihui Liu et al. Cancer Cell. .

Abstract

Mutations of ALK are frequently observed in MYCN-amplified neuroblastomas and correlate with poor clinical outcome, but how these oncogenes cooperate in neuroblastoma development remains unclear. In this issue of Cancer Cell, Zhu et al. describe a mechanism by which ALK and MYCN synergistically induce neuroblastoma in the zebrafish model system.

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Figures

Fig. 1
Fig. 1
MYCN and ALK F1174L synergistically impact neuroblastoma tumorigenesis. In zebrafish, the MYCN over-expression causes expansion of the sympathoadrenal neuroblasts from 3 to 5 wpf, and the MYCN over-expressing neuroblasts fail to differentiate into chromaffin cells. Only a small group of zebrafish (17%) with MYCN over-expression developed neuroblastoma, others won’t because MYCN over-expression also triggers an apoptotic response at 5.5 wpf. The activated ALK F1174L provides a cell survival signal that blocks the apoptotic response of MYCN-overexpressing neuroblasts at this juncture in development, so the tumor penetrance in the MYCN/ALK F1174L co-expressing transgenic fish is 3-fold higher (56%).
See this image and copyright information in PMC

Comment on

  • Activated ALK collaborates with MYCN in neuroblastoma pathogenesis.
    Zhu S, Lee JS, Guo F, Shin J, Perez-Atayde AR, Kutok JL, Rodig SJ, Neuberg DS, Helman D, Feng H, Stewart RA, Wang W, George RE, Kanki JP, Look AT. Zhu S, et al. Cancer Cell. 2012 Mar 20;21(3):362-73. doi: 10.1016/j.ccr.2012.02.010. Cancer Cell. 2012. PMID: 22439933 Free PMC article.

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References

    1. Azarova AM, Gautam G, George RE. Emerging importance of ALK in neuroblastoma. Semin Cancer Biol. 2011;21:267–275. - PMC - PubMed
    1. Hogarty MD, Maris JM. PI3King on MYCN to Improve Neuroblastoma Therapeutics. Cancer Cell. 2012;21:145–147. - PubMed
    1. Maris JM. Recent advances in neuroblastoma. N Engl J Med. 2010;362:2202–2211. - PMC - PubMed
    1. Mertz JA, Conery AR, Bryant BM, Sandy P, Balasubramanian S, Mele DA, Bergeron L, Sims RJ., 3rd Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A. 2011;108:16669–16674. - PMC - PubMed
    1. Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, Look AT. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science. 1994;263:1281–1284. - PubMed

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