Introduction. Multiple endocrine neoplasia type 2 (MEN2) is a rare syndrome, inherited in an autosomal dominant pattern, characterized by combination of medullary thyroid carcinoma with pheochromacytoma, tumors of the parathyroid glands and more rare tumors. Therefore, up till now there are no data about RET protooncogene mutations causing MEN2 syndrome in Lithuania.
The aim of the study. To determine and evaluate RET protooncogene mutations in patients with MEN2 syndrome in Lithuania. To determine frequency of MEN2 syndrome probands in patients with medullary thyroid carcinoma in Lithuania.
Methods. A total of 47 unrelated patients with medullary thyroid carcinoma were enrolled into the study. Patients underwent genetic testing by DNA sequencing, detecting germline mutations causing MEN2 syndrome.
Results. RET protooncogene mutations causing MEN2 syndrome were detected in 8 patients of the 47 medullary thyroid carcinoma cases – 17.02% (CI 95% 6.4 – 27.7%). The most frequent RET protooncogene mutations (in 611 (N2), 618(N1), 634 (N2) codons) were detected to cause MEN2A syndrome (62.5%), less frequent mutation in 918 codone (N2) that caused MEN2B syndrome, most rare – familial medullary thyroid carcinoma syndrome causative mutation in 791 codone (N1). In patients with detected MEN2 syndrome causative mutations in RET protooncogene, medullary thyroid carcinoma manifested in younger age – 29.8 ±16.1 years, comparing with sporadic cases – 49.5±10.7 years.
Conclusions. For the first time in Lithuania in unrelated patients with medullary thyroid carcinoma detected frequency of probands and germline RET protooncogene mutations causing MEN2 syndrome was 17.02 (CI 95% 6.4 – 27.7%). The study has also assessed the potential role of RET protooncogene mutations to the clinical features of medullary thyroid carcinoma.
Keyword(s): Multiple endocrine neoplasia type 2, MEN2 syndrome, RET protooncogene, genetic analysis.
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