MUTATIONAL ANALYSIS OF THE CDKN2 GENE IN METASTASES FROM PATIENTS WITH CUTANEOUS MALIGNANT-MELANOMA

We analysed 26 metastases from 25 patients with sporadic cutaneous mal ignant melanoma for alterations in the CDKN2 gene by a combined polyme rase chain reaction/single-strand conformation polymorphism (PCR/SSCP) /nucleotide sequencing approach. Eleven alterations (one in exon 1, fi ve in exon 2 and five in the 3' non-coding sequence of the exon 3 regi on) were concordantly and independently detected by both SSCP and nucl eotide sequence analysis. Two of the exon 2 changes and the five chang es in the non-coding exon 3 region are likely to represent natural pol ymorphism. Four (15%) of 26 metastases thus had CDKN2 mutations and be longed to 3 (12%) of 25 patients. Semi-quantitative PCR furthermore re vealed no sign of homozygous deletions of the CDKN2 exon 2 region. The results support an involvement of the CDKN2 product in the developmen t of a subgroup of sporadic melanomas and encourage the search for alt erations in additional genes of the 9p21 region.