SIMPLE TANDEM REPEAT ALLELIC DELETIONS CONFIRM THE PREFERENTIAL LOSS OF DISTAL CHROMOSOME 6Q IN MELANOMA

Karyotypic analysis, loss of somatic heterozygosity, microcell fusion and cDNA transfection studies have provided compelling evidence that a t least one tumour suppressor gene for melanoma resides on chromosome 6. In an attempt to further define the regions to which these putative suppressor genes map, we have carried out loss of heterozygosity (LOH ) studies on DNA from 25 fresh melanoma tumours for 9 simple tandem re peat (STR) polymorphism markers spanning chromosome 6. Four samples di splayed LOH or homozygosity for all markers studied, indicating that t hey had lost one homologue of chromosome 6. An additional 3 samples sh owed LOH for all markers on 6q. Furthermore, 30 melanoma cell lines, f or which there were no matching somatic DNA samples, were analyzed for hemizygosity of markers on 6q. One cell line had a homozygous deletio n of all markers tested and a further 12 cell lines displayed only one allele for 3 or 4 contiguous markers, indicating that most, if not al l of these samples were hemizygous for the region of 6q distal to D6S8 7. Overall, the rate of LOH on 6q in the 55 melanoma DNAs was 35%, and there were no losses of markers on 6p without concomitant loss of mar kers on 6q. Two of 5 samples derived from primary melanomas showed LOH , which indicates that LOH for the malanoma suppressor gene on 6q, whi ch maps to a region that contains the SOD2 locus, is a frequent and ea rly event in melanoma tumorigeneis. (C) 1994 Wiley-Liss, Inc.