Department of Immunology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland.
Laboratory of Cellular Immunology, Maria Sklodowska-Curie Institute - Oncology Center, W.K. Roentgen 5, 02-781, Warsaw, Poland.
Endocr Pathol. 2017 Sep;28(3):198-206. doi: 10.1007/s12022-017-9487-2.
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.
原癌基因 RET 胚系功能获得性突变是甲状腺癌发生和遗传性髓样甲状腺癌及 MEN2 综合征发生的起始原因。大多数 RET 突变都建立了基因型-表型相关性，但该基因同义突变的重要性仍存在争议。我们旨在分析波兰人群中的 RET 基因变异。对 585 名年龄在 1-85 岁的人进行了 RET 基因变异的基因检测，包括 448 名髓样甲状腺癌患者及其一级和二级亲属 131 名，以及 6 名疑似 MTC/MEN2 的患者。除了最常见的同义突变 p.Leu769Leu、p.Ser836Ser 和 p.Ser904Ser 外，在波兰人群中还发现了 RET 基因中的四个罕见突变 c.1827C>T(p.Cys609Cys)、c.2364C>T(p.Ile788Ile)、c.2418C>T(p.Tyr806Tyr)和 c.2673G>A(p.Ser891Ser)。其中两个罕见突变 p.Cys609Cys 和 p.Ile788Ile 以前未被描述过。通过对 400 名新生儿匿名血样的检测，评估了人群中分子同义变异的频率。我们的发现可能有助于更好地了解 RET 基因的遗传多样性以及同义变异在这种多样性中的作用。
