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Somatic mutation and loss of expression of a candidate tumor suppressor gene TET3 in gastric and colorectal cancers.
Mo, Ha Yoon; An, Chang Hyeok; Choi, Eun Ji; Yoo, Nam Jin; Lee, Sug Hyung.
Afiliação
  • Mo HY; Departments of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
  • An CH; General Surgery, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
  • Choi EJ; Departments of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
  • Yoo NJ; Departments of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
  • Lee SH; Departments of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea. Electronic address: suhulee@catholic.ac.kr.
Pathol Res Pract ; 216(3): 152759, 2020 Mar.
Article em En | MEDLINE | ID: mdl-31859118
Ten-eleven translocation 3 (TET3) is responsible for the DNA methylation and plays an important role in regulation of the gene expression. TET2, another TET, is frequently mutated in hematologic malignancies and considered a driver gene for leukemogenesis. TET3 mRNA downregulation has been identified in many solid cancers, suggesting its role as a candidate tumor suppressor gene (TSG). However, somatic inactivating mutation and protein expression in solid cancers are largely unknown. The aim of our study was to find whether TET3 gene was mutated and expressionally altered in gastric (GC) and colorectal cancers (CRC). TET3 gene possesses mononucleotide repeats in the coding sequence that could be mutated in cancers with high microsatellite instability (MSI-H). We analyzed 79 GCs and 124 CRCs, and found that GCs (2.9 %) and CRCs (7.6 %) with MSI-H, but not those with microsatellite stable/low MSI (MSS), harbored frameshift mutations within the repeats. In immunohistochemistry, loss of TET3 expression was identified in 32 % of GCs and 28 % of CRCs. Positive TET3 immunostaining in MSI-H cancers with TET3 frameshift mutation (1/7) was significantly lower than that without TET3 frameshift mutations (75/110). Our data may indicate TET3 harbored not only frameshift mutation but also loss of expression, which together could play a role in tumorigenesis of GC and CRC with MSI-H by inhibiting TSG functions of TET3.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Neoplasias Colorretais / Genes Supressores de Tumor / Dioxigenases Limite: Humans Idioma: En Revista: Pathol Res Pract Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Neoplasias Colorretais / Genes Supressores de Tumor / Dioxigenases Limite: Humans Idioma: En Revista: Pathol Res Pract Ano de publicação: 2020 Tipo de documento: Article