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Endocr Pathol. 2017 Sep;28(3):198-206. doi: 10.1007/s12022-017-9487-2.

Analysis of Newly Identified and Rare Synonymous Genetic Variants in the RET Gene in Patients with Medullary Thyroid Carcinoma in Polish Population.

Author information

1
Department of Immunology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland. maria.sromek@coi.pl.
2
Laboratory of Cellular Immunology, Maria Sklodowska-Curie Institute - Oncology Center, W.K. Roentgen 5, 02-781, Warsaw, Poland. maria.sromek@coi.pl.
3
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland.
4
Department of Oncology, The Children's Memorial Health Institute, Warsaw, Poland.
5
Department of Diagnostic Laboratory of Genetic Predispositions, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland.
6
Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland.
7
Department of Gastroenterological Oncology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland.
8
Genetic Counseling Unit, Cancer Prevention Center, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland.
9
Department of Immunology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland.

Abstract

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.

KEYWORDS:

MEN2; Medullary thyroid carcinoma; RET gene; Synonymous mutation; Thyroid

PMID:
28647780
PMCID:
PMC5552825
DOI:
10.1007/s12022-017-9487-2
[Indexed for MEDLINE]
Free PMC Article

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