GENETICS OF 7 DUTCH FAMILIAL ATYPICAL MULTIPLE MOLE MELANOMA SYNDROMEFAMILIES - A REVIEW OF LINKAGE RESULTS INCLUDING CHROMOSOME-1 AND CHROMOSOME-9

Familial atypical multiple mole-melanoma syndrome is characterized by the familial occurrence of malignant melanoma of the skin in combinati on with multiple atypical precursor nevi; its pattern shows a dominant inheritance in pedigrees. During the last 5 years we have performed l inkage analysis in seven Dutch familial atypical multiple mole-melanom a families to define the locus of the underlying gene defect. In 1989 it was reported that in familial melanoma families in the USA a diseas e-gene was located on chromosome Ip. However, in the Dutch families we could exclude this chromosome from harboring the Dutch familial atypi cal multiple mole-melanoma gene. Very recently a new candidate locus w as found on chromosome 9p, which could be confirmed in our family mate rial. A melanoma-associated gene was linked to several markers on chro mosome 9p21. In a linkage analysis in which only melanoma patients wer e considered as affected, marker D9S171 showed a maximum lod score of 3.11 (theta 0.0). After introducing family members with 10 or more, or five or more, atypical nevi as affected in addition to the melanoma p atients, the maximum lod score rose to 4.88 (theta 0.05) and 3.79 (the ta 0.07), respectively. Interestingly, the sharing of a unique chromos ome 9p21. haplotype among most melanoma patients in the families from two different villages suggests that an old common mutation is present in the Leiden region.