Loss of heterozygosity (LOH) in several chromosomal regions is found in melanoma, and it has been partially studied in nevi. BRAF mutations are found in melanoma and nevi and in colorectal cancer are linked to mismatch repair deficiency. We studied early genetic events involved in melanomagenesis through analysis of allelic loss, microsatellite instability (MSI), and BRAF mutations.
DNA extracted from microdissected cells of 22 common nevi, 23 atypical nevi, and 25 primary cutaneous melanomas were examined for LOH and MSI by polymerase chain reaction-based analysis of 24 microsatellite markers and BRAF mutation. Allelic loss index was higher in atypical nevi (0.20) and melanomas (0.27) than common nevi (0.07). LOH was frequent at 9p21, 17q21, 6q23, and 5q35 in melanoma. LOH at any of this loci occurred in 27% of common nevi, 57% of atypical nevi, and 68% of melanomas. BRAF mutations were not related to MSI presence and MSI index was not related with BRAF mutational status. Similar genetic alterations in atypical nevi and melanomas support the concept of atypical nevus as melanoma precursor. Novel deletion loci at 5q35 and 17q21 (BRCA1) in atypical nevi and melanomas were identified. Mismatch repair deficiency is not a crucial event for BRAF mutation in melanocytic tumors.