IDH1 p.R132 mutations may not be actively involved in the carcinogenesis of hepatocellular carcinoma

Jun Lu, Yang Zou, Ling Xu, Run Xiang Yang, Yu Fan, Wen Zhang, Dandan Yu, Yong Gang Yao

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Background: Recent studies have identified prevalent isocitrate dehydrogenase 1 (IDH1) codon 132 mutations (p.R132) in gliomas and acute myeloid leukemia (AML). The IDH1 mutations lead to a loss of its normal enzymatic activity and acquisition of neomorphic activity in production of a-ketoglutarate (a-KG) and 2-hydroxyglutarate (2-HG), which finally cause alterations of multiple gene expression of tumorigenesis-associated α-KG-dependent enzymes. The aim of this study was to determine whether IDH1 p.R132 mutations are involved in the carcinogenesis of hepatocellular carcinoma. Material/Methods: A total of 87 Han Chinese patients with primary hepatocellular carcinoma (HCC) were analyzed by direct DNA sequencing for IDH1 p.R132 mutations. The expression levels of multiple a-KG-dependent enzymes and associated genes were quantified in HepG2 cells overexpressing IDH1 p.R132 mutants by Western blotting and real- time PCR. Results: None of 87 Han Chinese patients with HCC harbored any IDH1 p.R132 mutations. The protein levels of HIF-1a and histone methylation marker (H3K4me3 and H3K79me2) were determined in HepG2 cells overexpressing IDH1 p.R132 mutants, but we discerned no difference. Measurement of mRNA expression levels of VEGF, GLUT1, and HOXA genes also showed no significant difference between cells overexpressing IDH1 wild-type and p.R132 mutants. Conclusions: Our negative results, together with some previous reports of the absence of IDH1 p.R132 mutations in HCC tissues, suggests that IDH1 p.R132 mutations are not actively involved in the development of HCC.

Original languageEnglish
Pages (from-to)247-254
Number of pages8
JournalMedical Science Monitor
Volume20
DOIs
StatePublished - 14 Feb 2014
Externally publishedYes

Keywords

  • Carcinogenesis
  • Carcinoma
  • Hepatocellular
  • Histones
  • Mutation-genetics

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