Background: Ret protooncogene germ-line mutations are associated with the inherited multiple endocrine neoplasia type 2 syndromes (MEN2a and MEN2b) and also with familial medullary thyroid carcinoma (FMTC). In this study, we report a large scale of mutations in exon 10, 11, 13 and 14 RET protoocogene in patients from Serbia. Our study included patients with MTC.
Methods: Our study included 180 patients. Patients were tested for RET protooncogene mutations in exons 10, 11, 13 and 14 by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) and sequencing analyses. Sequencing analysis was performed on ALFexpress II using Thermo Sequence CY5 Terminator Cycle Sequencing Kit and Applied Biosystem Genetic Analyzer 3130 using Big Dye Sequencing Kit.
Results: In 41/180 (23%) patients 7 different heterozygous germ-line mutations were identified: (C634Y, C634R, C634F, C634W in exon 11; C618Y in exon 10; Y791F in exon 13; and V804M in exon 14). Prophylactic thyroidectomy was performed in 6 C634R germline mutation carriers. Interestingly in one family with Y791F mutation MEN 2a was found while in other three components of brachi-oto-remal syndrome were found without MTC. Two patients with V804M had MTC.
Conclusions: Base on these data in Serbian population we found similar frequencies of inherited medullary thyroid carcinoma as in other European countries.