HAPLOTYPE ANALYSIS OF 2 RECURRENT CDKN2A MUTATIONS IN 10 MELANOMA FAMILIES - EVIDENCE FOR COMMON FOUNDERS AND INDEPENDENT MUTATIONS

Germ-line mutations in CDKN2A have been shown to predispose to cutaneo us malignant melanoma. We have identified 2 new melanoma kindreds whic h carry a duplication of a 24bp repeat present in the 5' region of CDK N2A previously identified in melanoma families fram Australia and the United States. This mutation has now been reported in 5 melanoma famil ies from 3 continents: Europe, North America, and Australasia, The M53 I mutation in exon 2 of CDKN2A has also been documented in 5 melanoma families from Australia and North America. The aim of this study was t o determine whether the occurrence of the mutations in these families from geographically diverse populations represented mutation hotspots within CDKN2A or were due to common ancestors. Haplotypes of 11 micros atellite markers flanking CDKN2A were constructed in 5 families carryi ng the M53I mutation and 5 families carrying the 24bp duplication. The re were some differences in the segregating haplotypes due primarily t o recombinations and mutations within the short tandem repeat markers; however, the data provide evidence to indicate that there mere at lea st 3 independent 24bp duplication events and possibly only 1 original M53I mutation. This is the first study to date which indicates common founders in melanoma families from different continents. (C) 1998 Wile y-Liss, Inc.