LINKAGE ANALYSIS IN DUTCH FAMILIAL ATYPICAL MULTIPLE MOLE MELANOMA (FAMMM) SYNDROME FAMILIES - EFFECT OF NEVUS COUNT

Familial atypical multiple mole-melanoma (FAMMM) syndrome is character ized by the familial occurrence of malignant melanoma of the skin in c ombination with multiple atypical precursor naevi. In the present stud y we performed linkage analysis in seven Dutch FAMMM families to defin e the relationship between the ultimate phenotype melanoma and the pos tulated precursors, atypical (dysplastic) naevi. Various models were d efined, varying from melanoma only to various combinations of melanoma and atypical naevi, reflecting the FAMMM phenotype. Using 124 microsa tellite markers spread across all autosomes, hints for linkage were ob tained between several chromosome 9p markers and a melanoma locus (D9S 171; odds for linkage, 275:1). In a model including melanoma and a flo rid manifestation of atypical naevi a considerably higher lod score wa s obtained with D9S171 (odds for linkage, 4365:1); models including mi lder manifestations yielded less support. We conclude that, also in th e Dutch FAMMM families, a melanoma gene is located on the short arm of chromosome 9 and that multiple atypical naevi, at least in certain ca ses, seems to be a component of the FAMMM phenotype.