Alternative titles; symbols
SNOMEDCT: 447888006; ORPHA: 276148; DO: 452;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 8q12.1 | Adenomas, salivary gland pleomorphic, somatic | 181030 | 3 | PLAG1 | 603026 |
A number sign (#) is used with this entry because of evidence that the disorder can be caused by t(3;8)(p21;q12) translocations that result in a fusion between pleomorphic adenoma gene-1 (PLAG1; 603026) and the beta-1-catenin gene (CTNNB1; 116806) and the TCEA1 gene (601425).
Pleomorphic salivary gland adenoma (PSA) is the most common tumor of the human parotid gland. It is a benign, slow-growing tumor, but local recurrences are observed. Mark and Dahlenfors (1986) and Bullerdiek et al. (1987) found clonal chromosome abnormalities, with a preponderance of aberrations involving 8q12.
Bullerdiek et al. (1987) found another subgroup of tumors characterized by changes affecting 12q13-q15. This subgroup was found in 9 of 40 PSAs and in 9 cases reported in the literature.
Stenman et al. (1989) used monoclonal antibodies to study the expression of p21(RAS) in benign and malignant salivary gland tumors, as well as in normal salivary gland tissue. They found that 28 of 29 benign pleomorphic adenomas overexpressed p21(RAS), whereas only 12 of 18 malignant salivary gland tumors expressed the p21 protein. The expression levels were also substantially higher in the adenomas than in the malignant tumors. They showed a correlation between levels of p21 expression and the karyotype of the pleomorphic adenomas indicating a relationship to chromosome 8 rearrangement. Stenman et al. (1989) hypothesized that a gene located at 8q12 is involved in the regulation of RAS gene expression.
Astrom et al. (1999) demonstrated that PLAG1 activation in salivary gland tumors can occur without microscopically apparent 8q12 abnormalities, i.e., a grossly normal karyotype, and that the translocation elongation factor SII (TCEA1; 601425) is a fusion partner of the PLAG1 gene in some cases.
Asp et al. (2006) carried out RT-PCR analysis of 27 cytogenetically characterized pleomorphic salivary gland adenomas containing chromosome 8q12 translocations that lacked PLAG1/CTNNB1 (116806) gene fusions. They detected chimeric transcripts of CHCHD7 (611238) exon 1 fused to either exons 3 and 4 of PLAG1 or to PLAG1 exons 2 to 4 in 3 tumors: a tumor containing a t(8:15)(q12;q14) translocation, a second containing at t(6;8)(p22-21.3;q13) translocation, and a third tumor with a normal karyotype. Using immunohistochemistry of tumor tissues containing CHCHD7/PLAG1 fusions, Asp et al. (2006) detected PLAG1 protein and suggested that the CHCHD7/PLAG1 gene fusion upregulates PLAG1 protein expression.
Asp, J., Persson, F., Kost-Alimova, M., Stenman, G. CHCHD7-PLAG1 and TCEA1-PLAG1 gene fusions resulting from cryptic, intrachromosomal 8q rearrangements in pleomorphic salivary gland adenomas. Genes Chromosomes Cancer 45: 820-828, 2006. [PubMed: 16736500] [Full Text: https://doi.org/10.1002/gcc.20346]
Astrom, A.-K., Voz, M. L., Kas, K., Roijer, E., Wedell, B., Mandahl, N., Van de Ven, W., Mark, J., Stenman, G. Conserved mechanism of PLAG1 activation in salivary gland tumors with and without chromosome 8q12 abnormalities: identification of SII as a new fusion partner gene. Cancer Res. 59: 918-923, 1999. [PubMed: 10029085]
Bullerdiek, J., Bartnitzke, S., Weinberg, M., Chilla, R., Haubrich, J., Schloot, W. Rearrangements of chromosome region 12q13-q15 in pleomorphic adenomas of the human salivary gland (PSA). Cytogenet. Cell Genet. 45: 187-190, 1987. [PubMed: 3691185] [Full Text: https://doi.org/10.1159/000132452]
Bullerdiek, J., Raabe, G., Bartnitzke, S., Boschen, C., Schloot, W. Structural rearrangements of chromosome #8 involving 8q12--a primary event in pleomorphic adenomas of the parotid gland. Genetica 72: 85-92, 1987. [PubMed: 3505884] [Full Text: https://doi.org/10.1007/BF00123166]
Mark, J., Dahlenfors, R. Cytogenetical observations in 100 human benign pleomorphic adenomas: specificity of the chromosomal aberrations and their relationship to sites of localized oncogenes. Anticancer Res. 6: 299-308, 1986. [PubMed: 3707067]
Stenman, G., Sandros, J., Mark, J., Nordkvist, A. High p21(RAS) expression levels correlate with chromosome 8 rearrangements in benign human mixed salivary gland tumors. Genes Chromosomes Cancer 1: 59-66, 1989. [PubMed: 2562114] [Full Text: https://doi.org/10.1002/gcc.2870010110]