REFINED LOCALIZATION OF THE MELANOMA (MLM) GENE ON CHROMOSOME 9P BY ANALYSIS OF ALLELIC DELETIONS

Various lines of evidence including linkage analysis, frequent homozyg ous and heterozygous deletions in melanoma DNAs, and the finding of a patient with multiple primary melanomas who harbours a 5p/9p transloca tion involving loss of several 9p markers, have indicated that the 9p2 2-p13 region harbours a gene important for the development of melanoma (MLM). We have used eight short tandem repeat polymorphism (STRP) mar kers mapping to this region to look for allelic losses in DNA from mel anoma biopsies and cell lines. Heterozygous losses were found in 8/14 (57%) fresh melanoma biopsy DNAs with the smallest region of overlap ( SRO) being between IFNA and D9S169. In addition, when DNA from 30 mela noma cell lines was studied, four cell lines (13%) were found to be ho mozygously deleted for various 9p markers. Two of these cell lines def ine the borders of overlapping homozygous deletions within a 4cM regio n of 9p21 between IFNA and D9S171. Moreover, a further 14 melanoma cel l lines were hemizygous for the IFNA/ D9S171/D9S126 region. These data support the hypothesis that the MLM gene acts as a tumour suppressor, and provide a refinement of its localization on 9P.