ECE2021 Audio Eposter Presentations Thyroid (157 abstracts)
Molecular landscape of the multiple endocrine neoplasia type 2 syndrome in the Belarusian population
Yuliya Dydyshka 1 , Alla Shepelkevich 1 , Tatsiana Chakhovich 2 , Alina Shloma 2 , Sergey Smirnov 2 , Kseniya Ruksha 2 , Alena Subach 2 , Anna Portyanko 2 , Victor Kondratovich 3 , Tatiana Leonova 3 & Alexandra Sosedkova 3
1Belarusian State Medical University, Department of Endocrinology, Belarus; 2N.N. Alexandrov National Cancer Centre of Belarus, National Molecular Genetics Centre of Cancer Research, Belarus; 3Public Health Institution Minsk City Clinical Oncologic Dispensary, Belarus
Background
The multiple endocrine neoplasia syndrome type 2 (MEN-2) is characterized by medullary thyroid cancer (MTC) as a permanent feature; the combination with pheochromocytoma and parathyroidism is referred as MEN-2a syndrome. The reason for hereditary forms of MTC is mutations in the proto-oncogene RET (RE-arranged during Transfection).
The aim of the study was to establish the molecular determinants frequency of MEN-2 syndrome in patients with MTC in the Republic of Belarus.
Materials and methods
The study included 194 patients with MTC diagnosis. The selection was made according to the Cancer Register of the Republic of Belarus and the medical documentation of the Republican Center for Thyroid Tumors. Testing of 5, 8, 10, 11, 13–16 exons of the RET gene was performed by the method of molecular sequencing according to Sanger on the ABI 3500 genetic analyzer.
Results
From 1987 to 2017 years 26930 new cases of thyroid cancer were detected (4899 men and 22 031 women), the share of MTC was 2.2% (591 people). Genetically determined MTC with various clinical manifestations (MEN-2A, MEN-2B, familial MTC) was detected in 18.6% of cases (36/194). Pathogenic mutations were detected in exons 11, 13, and 10 of the RET gene (78%). Analysis of the gene disorders spectrum showed predominance in codon 634 of exon 11 of the gene (C634R\F\W\Y), which is associated with the development of familial MTC or MEN-2A syndrome. Rarer alterations are presented by polymorphisms Y791F, C620GW, L790F, S649L, V804M/L, S904F, R912P, M918T. The pathogenic variants L790F and C611Y were compiled for one case. Pathogenic variants in 634 codons were detected in 27.8% of cases (n = 10). The penetrance of pheochromocytoma was 50.0% (n = 5), the average age was 31.9 years. Among patients with mutations in other codons of the RET proto-oncogene, pheochromocytoma was found in one case (2.7%) in a patient with variant M918T. The penetrance of pheochromocytoma in patients with this pathogenic variant (n = 2) was 50.0%. A genotype–phenotype correlation was found between the presence of pheochromocytoma and mutations in exon 11 of the RET proto-oncogene (P = 0.009).
Conclusions
High frequency of occurrence of hereditary forms of MTC was found in the Republic of Belarus, similar to the spectrum of mutations in the RET proto-oncogene described in the literature, and the presence of a genotype-phenotype correlation in identifying various variants of gene alterations. The presented data are intermediate and will be clarified in the course of further implementation of research work.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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