Allelotypes of primary cutaneous melanoma and benign melanocytic nevi.
A multistep genetic model of tumorigenesis, based on genetic alterations in benign and primary malignant lesions, has been proposed for neoplasms such as colonic carcinoma. However, evidence for a similar genetic progression in melanoma has relied heavily on findings in cultured lesions or metastases. We have investigated every autosomal arm for loss of heterozygosity in 41 primary cutaneous melanomas and 32 benign melanocytic nevi, and have investigated several chromosome arms that show loss in melanoma in 27 Spitz nevi (a nevus with histological similarities to melanoma). Loss of heterozygosity in primary melanoma was identified most frequently on chromosomes 9p (46%) at loci near the p16INK4 gene, 10q (31%), 6q (31%), and 18q (22%); loss of these chromosome arms were related to the progression of the melanoma. Only two benign melanocytic nevi (both of which showed atypical features on histology) demonstrated genetic alterations, including p9 loss in one case. In addition, two Spitz nevi contained interstitial deletions on chromosome 9p. Our findings show that loss of heterozygosity of 9p is not confined to melanoma, but that other uncultured melanocytic lesions can also display loss of this chromosome arm, and that other genetic changes (e.g., loss of 10q, 6q, and 18q) may be important in conveying the malignant phenotype to melanoma.
Healy
E
E
Department of Dermatology, University of Newcastle upon Tyne, United Kingdom.
Belgaid
C E
CE
Takata
M
M
Vahlquist
A
A
Rehman
I
I
Rigby
H
H
Rees
J L
JL
D000483:Alleles; D002899:Chromosomes, Human, Pair 9; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D009508:Nevus, Pigmented / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm