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Deletion mapping suggests that the 1p22 melanoma susceptibility gene is a tumor suppressor localized to a 9-Mb interval

Walker, Graeme J., Indsto, James O., Sood, Raman, Faruque, Mezbah U., Hu, Ping, Pollock, Pam M., Duray, Pual, Holland, Elizabeth A., Brown, Kevin, Kefford, Richard F., Trent, Jeffrey M., Mann, Graham J., & Hayward, Nicholas K. (2004) Deletion mapping suggests that the 1p22 melanoma susceptibility gene is a tumor suppressor localized to a 9-Mb interval. Genes Chromosomes Cancer, 41(1), pp. 56-64.

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Abstract

Loss of the short arm of chromosome 1 is frequently observed in many tumor types, including melanoma. We recently localized a third melanoma susceptibility locus to chromosome band 1p22. Critical recombinants in linked families localized the gene to a 15-Mb region between D1S430 and D1S2664. To map the locus more finely we have performed studies to assess allelic loss across the region in a panel of melanomas from 1p22-linked families, sporadic melanomas, and melanoma cell lines. Eighty percent of familial melanomas exhibited loss of heterozygosity (LOH) within the region, with a smallest region of overlapping deletions (SRO) of 9 Mb between D1S207 and D1S435. This high frequency of LOH makes it very likely that the susceptibility locus is a tumor suppressor. In sporadic tumors, four SROs were defined. SRO1 and SRO2 map within the critical recombinant and familial tumor region, indicating that one or the other is likely to harbor the susceptibility gene. However, SRO3 may also be significant because it overlaps with the markers with the highest 2-point LOD score (D1S2776), part of the linkage recombinant region, and the critical region defined in mesothelioma. The candidate genes PRKCL2 and GTF2B, within SRO2, and TGFBR3, CDC7, and EVI5, in a broad region encompassing SRO3, were screened in 1p22-linked melanoma kindreds, but no coding mutations were detected. Allelic loss in melanoma cell lines was significantly less frequent than in fresh tumors, indicating that this gene may not be involved late in progression, such as in overriding cellular senescence, necessary for the propagation of melanoma cells in culture.

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22 citations in Web of Science®

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ID Code: 45827
Item Type: Journal Article
Keywords: Base Sequence, Chromosome Mapping, Chromosomes, Human, Pair 1, Genes, Tumor Suppressor, Genetic Linkage, Genetic Predisposition to Disease, Genotype, Humans, Lod Score, Loss of Heterozygosity, Melanoma/ genetics, Sequence Deletion
DOI: 10.1002/gcc.20056
ISSN: 1045-2257
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Divisions: Past > Schools > Cell & Molecular Biosciences
Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2004 Wiley-Liss, Inc.
Deposited On: 15 Sep 2011 05:50
Last Modified: 15 Sep 2011 05:51

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