The Comparison of Hotspot Mutations in Primary and Metastatic Melanoma Cell Lines

Objective: Melanoma is a disease that develops as a result of UV radiation acting as a mutagenic risk factor and causes various genetic changes. In our study, we aimed to determine the changes in human cancer-related genes between Primary Melanoma (WM115) and Metastatic Melanoma (SK-MEL-30) cell lines. Materials and Methods: Among the proto-oncogenes and tumor suppressor genes, 50 genes associated with human cancers were selected. Afterwards, the changes of hotspot mutations occurring in 50 genes between the two cell lines were examined using the Ion Ampliseq Cancer Hotspot DNA Panel v2 gene panel. Results: A mutation increase was observed in the metastatic melanoma cell line compared to the primary cell line. 4 Variant of Uncertain Significance (VUS), 3 benign and 2 pathogenic mutations were detected in the WM115 cell line. Pathogenic mutations have been identified in the BRAF proto-oncogene. In the SK-MEL-30 cell line, 24 VUS, 1 benign, and 1 possible pathogenic mutation (in the VHL gene) were observed. Conclusions: According to the results of our research, we think that the occurrence of BRAF mutations in primary melanoma indicates that this gene is effective in the progression and development of melanoma, and the mutation occurring in the VHL gene of metastatic melanoma might be effective in carcinogenesis via the HIF pathway. In addition, most of the VUS mutations of metastatic melanoma occurred in the RET and NOTCH pathways. The accumulation of mutations in genes involved in these pathways may contribute to the development of metastasis.