Oncogene mutations in cutaneous melanomas of different origin

Abstract

Melanoma is the most lethal malignancy of skin, which is characterized with clinical and molecular heterogeneity. The main role in melanoma carcinogenesis belongs to mitogen-activated protein kinase MAPK signaling pathway, which is hyperactivated mostly due to BRAF and NRAS mutations. Aim of the study was the analysis of oncogene mutations in melanomas of different origin. BRAF mutations were found in 60,4%, NRAS in 15,6% and KIT in 1% of tumor samples, most of which were regional metastases. The frequency of BRAF mutations were higher in tumors developed on trunk and extremities (69%), then in melanomas located on face and head with chronic UV exposure (44%). NRAS mutations were more common- in melanomas on face (33%) and low extremities (28%), then in tumors on trunk. BRAF mutations were found in 70% of patients younger 40 years while the median age for the group of patients with NRAS mutations was 62 years. There were no differences in frequency of oncogene mutations observed in pigmented and amelanotic tumors, as well as superficial spreading and nodal melanоmas. Cutaneous melanomas have prevalently epithelioid phenotype and BRAF и NRAS mutation frequencies in epithelioid melanomas were higher than in spindle cell and nevoid ones. Thus BRAF и NRAS mutations are associated with location of primary melanoma, histologic type of tumor and age of patients.