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, Paul, Holland, Elizabeth A., Brown, Kevin, Kefford, Richard F., Trent, Jeffrey M., Mann, Graham J. and 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: 56-64. doi:10.1002/gcc.20056

Author Walker, Graeme J.
Indsto, James O.
Sood, Raman
Faruque, Mezbah U.
Hu, Ping
Pollock, Pam M.
Duray, Paul
Holland, Elizabeth A.
Brown, Kevin
Kefford, Richard F.
Trent, Jeffrey M.
Mann, Graham J.
Hayward, Nicholas K.
Title Deletion mapping suggests that the 1p22 melanoma susceptibility gene is a tumor suppressor localized to a 9-Mb interval
Journal name Genes, Chromosomes & Cancer   Check publisher's open access policy
ISSN 1045-2257
Publication date 2004-09-01
Sub-type Article (original research)
DOI 10.1002/gcc.20056
Volume 41
Issue 1
Start page 56
End page 64
Total pages 9
Editor F. Mitelman
J. D. Rowley
Place of publication Hoboken, U.S.A.
Publisher Wiley-Liss
Language eng
Subject C1
730108 Cancer and related disorders
1112 Oncology and Carcinogenesis
Formatted 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.
© 2004 Wiley-Liss, Inc.
Keyword Oncology
Genetics & Heredity
Cutaneous Malignant Melanomas
Chromosome Arm 1p
Heterozygosity Analysis
Allelic Deletions
Cell Lines
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2005 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 27 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 26 times in Scopus Article | Citations
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Created: Wed, 15 Aug 2007, 13:05:30 EST