Abstract

Background/aim: Malignant melanoma is the most common cause of death due to skin cancers. The most common mutations in RAFRAS pathway from tumor oncogenes are BRAF and NRAS. In this study, we analyzed the frequency of BRAF and NRAS gene mutations and investigated their association with clinicopathological features of melanomas in the Turkish population. Materials and methods: 65 primary cutaneous melanoma were included in the study. The mutations were evaluated with real-time PCRbased PCR-array through allele-specific amplification, and the results were correlated with various clinicopathological characteristics. Results: 52.3% of the patients were female and 47.7% were male. The mean age of the patients with a mutation was lower than those without mutation. 16 patients had BRAF mutation. 12 patients had NRAS mutation. NRAS mutation was statistically more common in men (P = 0.036). The number of mitoses increased with the increase of the tumor thickness (P = 0.003). There was more mitosis in the presence of ulceration (P = 0.05). A total of 41.7% of NRAS mutations had adjuvant chemotherapy. Conclusion: We found lower mutation rate when compared to regional studies. NRAS mutation was common in men. This is the first study from our region evaluating the prognostic value of clinical stage and necessity of adjuvant treatment with the presence of BRAF and NRAS mutations.

Highlights

  • The incidence of malignant melanoma (MM) of the skin has steadily increased in the past decades [1]

  • This is the first study from our region evaluating the prognostic value of clinical stage and necessity of adjuvant treatment with the presence of BRAF and NRAS mutations

  • The number of mitoses increased with the increase of tumor thickness, and mitosis was more common with the presence of ulceration (P = 0.003 and P = 0.05)

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Summary

Introduction

The incidence of malignant melanoma (MM) of the skin has steadily increased in the past decades [1]. Stem cell growth factor receptor (KIT) and mitogenactivated protein kinase (MAPK) cascade including RAS-RAF-MEK-ERK are important pathways mediating cellular responses to growth signals regulating cell proliferation, survival, and differentiation [3]. KIT is a cytokine receptor that is expressed on the surface of melanocytes. Altered forms of this receptor are associated with some melanoma types [4]. NRAS and BRAF mutations are mainly involved in the pathogenesis of melanoma. BRAF is a member of the RAF kinase family of growth signal transduction protein kinases and it takes part in regulating the MAPK pathway [5]. NRAS is a member of RAS family of GTPases and the most

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