LINKAGE OF CUTANEOUS MALIGNANT-MELANOMA DYSPLASTIC NEVI TO CHROMOSOME9P, AND EVIDENCE FOR GENETIC-HETEROGENEITY

We examined the relationship between cutaneous malignant melanoma/dysp lastic nevi (CMM/DN) and chromosome 9p in 13 pedigrees with two or mor e living cases of invasive melanoma. We used two highly informative (C A)(n) repeats, D9S126 and IFNA, previously implicated in familial mali gnant melanoma (MLM), to conduct linkage analysis. Three analyses were performed: (1) CMM alone-all individuals without either confirmed mel anoma or borderline lesions were considered unaffected (model A); (2) CMM/DN with both variable age at onset and sporadics (model B); and (3 ) CMM affecteds only-all individuals either without confirmed melanoma or with borderline lesions were designated ''unknown'' (model C). The re was significant evidence for linkage to IFNA in all three models. F or CMM alone, the maximum lod score (Z(max)) was 4.36 at theta =.10 fo r model A and 3.39 at theta =.10 for model C. For CMM/DN (model B), Z( max) = 3.05 at theta =.20. There was no significant evidence for linka ge between CMM alone or CMM/DN and chromosome 9p marker D9S126. In add ition, there was significant evidence for heterogeneity when a homogen eity test allowing for linkage to chromosome 9p or chromosome 3p or ne ither region was used. These results suggest that there is an MLM susc eptibility locus on chromosome 9p but that familial melanoma is hetero geneous and not all families with CMM/DN are linked to a locus in this region.