Search

A familial melanoma susceptibility locus (MLM) was identified on the short arm of chromosome 9 in a set of Utah and Texas kindreds. Subsequent confirmation was reported for a set of 26 Australian kindreds, a set of 7 Dutch kindreds, and a set of 13 NIH melanoma kindreds. The original localization report placed the locus near the IFNA-D9S126 interval on chromosome 9p. We report further localization using D9S171 and a newly developed marker, D9S736, both of which lie in the IFNA-D9S126 interval. Analysis of this set of kindreds places the melanoma susceptibility locus in a 2-cM region that is proximal to D9S736 and distal to D9S171.

Linkage analysis of ten Utah kindreds and one Texas kindred with multiple cases of cutaneous malignant melanoma (CMM) provided evidence that a locus for familial melanoma susceptibility is in the chromosomal region 9p13-p22. The genetic markers analyzed reside in a candidate region on chromosome 9p21, previously implicated by the presence of homozygous deletions in melanoma tumors and by the presence of a germline deletion in an individual with eight independent melanomas. Multipoint linkage analysis was performed between the familial melanoma susceptibility locus (MLM) and two short tandem repeat markers, D9S126 and the interferon-alpha (IFNA) gene, which reside in the region of somatic loss in melanoma tumors. An analysis incorporating a partially penetrant dominant melanoma susceptibility locus places MLM near IFNA and D9S126 with a maximum location score of 12.71. Therefore, the region frequently deleted in melanoma tumors on 9p21 presumably contains a locus that plays a critical role in predisposition to familial melanoma.