ALLELOTYPES OF PRIMARY CUTANEOUS MELANOMA AND BENIGN MELANOCYTIC NEVI

A multistep genetic model of tumorigenesis, based on genetic alteratio ns in benign and primary malignant lesions, has been proposed for neop lasms such as colonic carcinoma. However, evidence for a similar genet ic progression in melanoma has relied heavily on findings in cultured lesions or metastases. We have investigated every autosomal arm for lo ss of heterozygosity in 41 primary cutaneous melanomas and 32 benign m elanocytic nevi, and have investigated several chromosome arms that sh ow loss in melanoma in 27 Spitz nevi (a nevus with histological simila rities to melanoma). Loss of heterozygosity in primary melanoma was id entified most frequently on chromosomes 9p (46%) at loci near the p16( INK4) gene, 10q (31%), 6q (31%), and 18q (22%); loss of these chromoso me arms were related to the progression of the melanoma. Only two beni gn melanocytic nevi (both of which showed atypical features on histolo gy) demonstrated genetic alterations, including 9p loss in one case. I n addition, two Spitz nevi contained interstitial deletions on chromos ome 9p, Our findings show that loss of heterozygosity of 9p is not con fined to melanoma, but that other uncultured melanocytic lesions can a lso display loss of this chromosome arm, and that other genetic change s (e.g., loss of 10q, 6q, and 18q) may be important in conveying the m alignant phenotype to melanoma.