Loss of polymorphic restriction fragments in malignant melanoma: implications for tumor heterogeneity.

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Abstract
Loss of genetic material at certain chromosomal sites is implicated in the etiology of retinoblastoma and Wilms tumor. Whether specific chromosomal deletions are associated with other types of human cancer needs to be explored. Melanoma cell lines (24), derived from 21 patients with nonfamilial malignant melanoma, were examined for evidence of somatically induced hemizygosity or homozygosity. DNA probes (12), recognizing single-copy restriction fragment length polymorphisms (RFLP) determined by loci on 11 different chromosomes, were used to screen autologous combinations of melanoma cells and either B cells or fibroblasts. Loss of heterozygosity in melanoma cells was identified at 27 of 100 informative loci. These losses occurred at loci on 8 different chromosomes, and the frequency of loss at individual loci varied between 8% and 67%. Somatic mutations resulting in homozygosity or hemizygosity are common in melanoma and evidently not restricted to specific chromosomes.