Assignment of a Locus for Familial Melanoma, MLM, to Chromosome 9p13-p22

Abstract

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.

Evidence for an Inherited Predisposition Contributing to the Risk for Rotator Cuff Disease

“…The Utah Population Database is a combination of a computerized genealogy of the Utah pioneers and their descendants with various data including the Utah Cancer Registry, Utah death certificates, and the University of Utah Hospital and Clinics 10 . This resource has been used to define the genetic contribution to many other phenotypes and was the basis of the identification in Utah pedigrees of BRCA1, BRCA2, and p16 [28][29][30] . Using this resource and similar methodology, we explored the hypothesis of a genetic contribution to rotator cuff disease and have shown a strong genetic predisposition for disease development.…”

cDNA array technology in melanoma: An overview

“…Loss of the chromosome regions 9p21 and 10q are usually considered the earliest changes in melanoma progression, while alterations or deletions involving regions 6q and 11q occur in correspondence of the RGP (Radial Growth Phase) to VGP (Vertical Growth Phase) conversion, and deletions on 1p, and amplification of 7q usually occur last (Fountain et al, 1990;Healy et al, 1995Healy et al, , 1996Walker et al, 1995;Robertson et al, 1996;Bastian et al, 1998). In particular, linkage analysis of familial melanoma has suggested the presence of a melanoma susceptibility gene on chromosome 9p21, which harbors the gene CDKN2A, encoding for a protein called p16 INK4A (Cannon-Albright et al, 1992;Rocco and Sidransky, 2001). The loss of heterozygosity for this gene is one of the earliest events in melanoma development, as the deletion is detected in invasive primary lesions with thin tumor thickness (Healy et al, 1996).…”

Alterations of p16 and p15 genes in acute leukemia with MLL gene rearrangements and their correlation with clinical features

“…[1][2][3] The p16 gene (also referred to as MTS1, INK4A, CDK4I or CDKN2) and p15 gene (also referred to as MTS2 or INK4B), which share extensive nucleotide sequence homology and are closely linked on 9p21, have been suggested to be new tumor suppressor genes by several investigators. The proteins encoded by p16 and p15 are key factors in the negative control of cell proliferation in that they inhibit the activity of two cyclindependent kinases (CDKs), CDK4 and CDK6.…”