The Investigation of putative genetic alterations and microsatellite instabilities in melanocytic nevi and malignant melanoma by using cytogenetic and molecular genetic techniques

Microsatellite instability Genetic alterations which occur in benign melanocytic nevi and malignant melanoma (MM) follow the multistep genetic model of the tumorigenesis. In this study, it was aimed to find out probable genetic alterations in melanocytic nevi and melanoma samples by using the molecular and cytogenetic procedures. Cytogenetic analysis was carried out via the cell cultures, prepared from nine MM and six melanocytic nevi, totally 15 different tissue samples. All of the melanocytic nevi was evaluated as cytogenetically normal. However, among the malignant melanoma cases, one had two clonal translocations 46,XX t (7; 12) (q22;q24), t (2; 11) (p25;q22), and the other case represented the karyotype of 47,XX + marker. The translocation breakpoints are in accordance with the similar findings in literature. The DNA samples, isolated from totally 21 paraffin blocks; four dysplastic nevi (DN), four compound nevi, seven MM and six congenital nevi, were amplified with PCR method by using four different microsatellite markers. Silver staining was used to investigate the allelic bands, and the following changes was observed : i) LOH (Loss of heterozygosity) in two MM tissue and MIN (Microsatellite instability) in a DN tissue with D2S 123 marker, ii) MIN in a DN tissue with D14S65 marker, iii) MIN in a DN tissue with BAT40 marker, iv) LOH in a MM tissue and MIN in a DN tissue with Dİ 1S29 marker. Some genetic alterations was noticed in 7 out of 21 samples (34 %). D2S123 marker is localized nearby a mismatch repair gene and the LOH may contribute to the loss of repair gene activity. This finding is indicative of mutator phenotype. Genetic alterations (LOH and MIN) are found in two different cases with Dİ 1S29 marker as well. This result claims that a probable tumor suppressor gene that can affect some other cancer types, either, might be present at the 1 lq23.3 locus.