Herediter melanomda CDKN2A ve MC1R germline gen mutasyonlarının araştırılması

Abstract

Çakır A., CDKN2A and MC1R Germline Gene Mutations in Hereditary Melanoma, Hacettepe University Faculty of Medicine, Skin and Venereal Diseases, Master’s Thesis, Ankara, 2018. Cutaneous melanoma is a malignant tumor that originates from the melanocytes of the skin. Phenotypical features such as fair skin and eye color and environmental factors, primarily ultraviolet play important role in the development of melanoma. Approximately 5-10% of melanomas develop due to genetic factors and these types of melanomas are called hereditary melanomas. CDK2NA mutations are responsible for 40% of hereditary melanoma cases worldwide. Mutations in MC1R gene increase the penetration of CDKN2A. There is a lack of data concerning the genetic features of melanoma patients in Turkey. The aim of this study was to define the phenotypical and genotypical features that differentiate hereditary melanomas from sporadic melanomas. For this purpose, using a modified scoring system, 31 patients who were designated to the hereditary melanoma group, and 12 patients who were designated to the sporadic melanoma group were included in this study. All patients were evaluated dermatologically in detail for phenotypical features, and CDKN2A and MC1R germline gene mutations were detected with Sanger sequencing method. Concerning phenotypic features, a statistically significant difference was found between the fair eye color and the sporadic melanoma (p=0.000). CDKN2A mutation was detected in only one patient in the hereditary melanoma group (3.2%); whereas no patient in the sporadic melanoma group had CDKN2A mutation. MC1R mutations were found in 25 out of 31 (80.6%) in the hereditary melanoma group, whereas this ratio was 41.7% in the sporadic melanoma group (p=0.024). The results of this study revealed that the most significant phenotypical risk factor for sporadic melanoma was the fair eye color. The results also suggested that CDKN2A might not be the dominant melanoma predisposition gene in Turkey. The difference between the two groups in terms of MC1R mutations supports the idea that MC1R genetic testing might be utilized to determine hereditary melanoma. Key Words: Melanoma, hereditary melanoma, CDKN2A, MC1R, germline mutation Supporting foundation: Hacettepe University Faculty of Medicine, Scientific Search Projects Support Unit, project number: 16087