GERMLINE P16 MUTATIONS IN FAMILIAL MELANOMA

The p16 gene is located in chromosome 9p21, a region that is linked to familial melanoma and homozygously deleted in many tumour cell lines. We describe eight p16 germline substitutions (one nonsense, one splic e donor site and six missense) in 13/18 familiar melanoma kindreds. Si x of these mutations were identified in 33/36 melanoma cases in nine f amilies, whereas two were detected in normal controls and are not dise ase-related. The melanoma-specific mutations were detected in 9p21-lin ked, but not in 1p36-linked, families, thereby confirming previous rep orts of genetic heterogeneity. Functional analyses of these mutations will confirm those causally related to the development of familial mel anoma.