CDKN2A (P16(INK4a)) and CDK4 mutation analysis in 131 Australian melanoma probands: Effect of family history and multiple primary melanomas

Mutation analysis of two genes involved in melanoma susceptibility (CDKN2A/ p16(INK4a) and CDK4) was undertaken in 131 probands with a family history o f melanoma. Screening of all three exons of CDKN2A and exon 2 of CDK4 by si ngle-strand conformation polymorphism (SSCP) analysis and/or direct sequenc ing identified a total of 10 different CDKN2A germline mutations, including 6 not previously described in the germline. All but one has been previousl y proven to, or is likely to, affect the structure and function of p16(INK4 a). The incidence of CDKN2A mutation was 8.4% (11/131), but was significant ly higher in families with three or more cases of melanoma (10/66, 15.1%) t han in those in which only two relatives were affected (1/65, 1.5%). The in cidence of CDKN2A mutation was also higher in families with three or more c ases of melanoma and at least one member with multiple primary melanomas (6 /19, 31.6%) than in similar families without multiple primary melanomas (4/ 47, 8.5%). One novel CDK4 variant of uncertain significance was found in a kindred that also carries a CDKN2A mutation. Genes Chromosomes Cancer 25:33 9-348, 1999. (C) 1999 Wiley-Liss, Inc.