LOSS OF HETEROZYGOSITY IN SPORADIC PRIMARY CUTANEOUS MELANOMA

Difficulties in obtaining clinical samples from primary melanomas have meant that most genetic analyses of melanoma have concentrated on cel l lines and metastases. Because the Breslow thickness of the primary t umour is the single best prognostic indicator, it is important to iden tify genetic abnormalities in primary melanomas and relate these chang es to the thickness of the lesion. We have investigated 47 sporadic me lanomas, of which 41 were primary lesions, for loss of heterozygosity (LOH) on several chromosomal arms, including areas where genes involve d in familial melanoma and other relevant hereditary syndromes map, an d where LOH has previously been reported in cell lines or metastatic l esions. LOH was identified at 66 (18%) of 358 informative loci in prim ary melanomas, and there was a significant relationship between the ov erall frequency of LOH and Breslow thickness (P < 0.0005). Loss of chr omosome arm 9p was most frequent, occurring in 15 (47%) of 32 informat ive primary tumours, and was observed in 3 of 11 informative lesions l ess than or equal to 1.5 mm in depth. LOH on chromosome arms 3p, 6q, 1 0q, 11q, and 17p was also relatively frequent, with loss of 3p and 10q heterozygosity in lesions less than or equal to 1.5 mm in depth, whil e LOH on 6q, 11q, and 17p was only detected in more invasive tumours. The results suggest that loss of these chromosome regions are importan t in sporadic cutaneous melanoma, and are consistent with chromosome a rm 9p loss occurring before loss of other chromosome arms. (C) 1995 Wi ley-Liss, Inc.