Analysis of Newly Identified and Rare Synonymous Genetic Variants in the RET Gene in Patients with Medullary Thyroid Carcinoma in Polish Population.
Gain-of-function germline mutations of the RET proto-oncogene are responsible for initiation of carcinogenesis within the thyroid gland and development of hereditary form of medullary thyroid carcinoma and MEN2 syndrome. Genotype-phenotype correlations are established for most RET mutations, but the importance of the synonymous changes in this gene remains debatable. We aimed to analyze RET gene variants in Polish population. Genetic testing for the RET gene variants was performed with standard methods in 585 people aged 1-85, including 448 patients with medullary thyroid carcinoma and 131 of their first- and second-degree relatives, as well as six patients suspected of MTC/MEN2. Besides the most frequent synonymous changes, p.Leu769Leu, p.Ser836Ser, and p.Ser904Ser, four rare changes-c.1827C>T (p.Cys609Cys), c.2364C>T (p.Ile788Ile), c.2418C>T (p.Tyr806Tyr), and c.2673G>A (p.Ser891Ser)-were found in the RET gene, in the Polish population. Two of the rare changes, p.Cys609Cys and p.Ile788Ile, had not been previously described. The frequency of molecular synonymous variants in the general population was evaluated by testing 400 anonymous blood samples of neonates. Our findings may contribute to a better understanding of the genetic diversity of the RET gene and the involvement of synonymous variants in this diversity.
['Sromek|Maria|M|', 'Czetwertyńska|Małgorzata|M|', 'Tarasińska|Magdalena|M|', 'Janiec-Jankowska|Aneta|A|', 'Zub|Renata|R|', 'Ćwikła|Maria|M|', 'Nowakowska|Dorota|D|', 'Chechlińska|Magdalena|M|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D018278:Carcinoma, Neuroendocrine D002648:Child D002675:Child, Preschool D004252:DNA Mutational Analysis D005260:Female D020022:Genetic Predisposition to Disease D018095:Germ-Line Mutation D006801:Humans D007223:Infant D008297:Male D008875:Middle Aged D018813:Multiple Endocrine Neoplasia Type 2a D011044:Poland D000090063:Proto-Oncogene Mas D051096:Proto-Oncogene Proteins c-ret D013964:Thyroid Neoplasms D055815:Young Adult
RET gene Medullary thyroid carcinoma Thyroid MEN2 Synonymous mutation