MUTATIONS IN THE CDKN2A (P16(INK4A)) GENE IN MICRODISSECTED SPORADIC PRIMARY MELANOMAS

The role of the CDKN2A (p16(INK4a)) gene in sporadic primary melanomas has remained unclear due to the inadequate number of mutational studi es. In the present study, we analyzed the entire coding region of the CDKN2A gene in microdissected sporadic primary melanomas, for the pres ence of mutations and polymorphisms, using 2 independent methods of mu tation detection, SSCP and CMC. We found II intragenic mutations in 8 melanomas out of 31 (26%) and the majority of mutations were located i n exon 1, with 2 cases harbouring multiple mutations. Of the mutations detected, 6 were C-to-T transitions, 4 involving CC sites; 2 melanoma s showed a novel deletion of one of the two 24-bp repeat units located at the 5' end of exon 1. There was also a high frequency of C-to-G an d C-to-T polymorphisms at the nucleotides 540 (frequency of G allele: 0.18) and 580 (frequency of T allele: 0.13) in the 3' untranslated reg ion. (C) 1998 Wiley-Liss, Inc.