Abstract
Medullary thyroid carcinoma (MTC) is a rare malignant tumor originating from parafollicular cells. In most cases, it occurs sporadically, but a hereditary form is also possible. Hereditary forms show autosomal dominant inheritance pattern. MTC can be either isolated or as a part of MEN2 syndromes. RET proto-oncogene mutations are responsible for both MTC and MEN2. The RET proto-oncogene comprises 21 exons and is located at 10q11.2. Mutations of RET may also lead to papillary thyroid carcinoma, lung cancer, chronic myelomonocytic leukemia, and familial Hirschsprung’s disease. In this study, we investigated RET mutation spectrum in patients who were referred to our laboratory for RET molecular analysis. Between the period of 2009-2014, 155 patients with MTC were referred to our molecular genetics laboratory for RET mutation analysis. Exons 10, 11, 13, 14, 15, 16 of the RET proto-oncogene were sequenced using Sanger sequencing method. 12 different RET mutations were detected in 32 cases (20.6%). The mutations detected and their frequencies were as follows: 28% C634Y (9 cases), 25% C634R (8 cases), 6% D631Y, S891A, M918T, C618S, V804M (2 cases), and 3% C618G, L790F, C611Y, K710R, S649L (1 case). As a conclusion, the majority of patients with hereditary MTC showed RET mutations located at exon 11. The most frequent two mutations in Turkish MTC patients were found in codon 634 which was consistent with the literature. The K710R mutation in RET gene was defined for the first time in this study.
Keywords: Medullary thyroid carcinoma, RET gene, DNA sequencing, hereditary disease, mutation
