Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus

A locus for familial melanoma, MLM , has been mapped within the same interval on chromosome 9p21 as the gene for a putative cell cycle regulator, p16 INK4 ( CDKN2 ) MTS1. This gene is homozygously deleted from many tumour cell lines including melanomas, suggesting that CDKN2 is a good candidate for MLM . We have analysed CDKN2 coding sequences in pedigrees segregating 9p melanoma susceptibility and 38 other melanoma-prone families. In only two families were potential predisposing mutations identified. No evidence was found for heterozygous deletions of CDKN2 in the germline of melanoma-prone individuals. The low frequency of potential predisposing mutations detected suggests that either the majority of mutations fall outside the CDKN2 coding sequence or that CDKN2 is not MLM .