Mutation and expression analysis of the IDH1, IDH2, DNMT3A, and MYD88 genes in colorectal cancer

Gene. 2014 Aug 10;546(2):263-70. doi: 10.1016/j.gene.2014.05.070. Epub 2014 Jun 2.

Abstract

Colorectal cancer (CRC) is one of the leading causes of death around the world. Its genetic mechanism was intensively investigated in the past decades with findings of a number of canonical oncogenes and tumor-suppressor genes such as APC, KRAS, and TP53. Recent genome-wide association and sequencing studies have identified a series of promising oncogenes including IDH1, IDH2, DNMT3A, and MYD88 in hematologic malignancies. However, whether these genes are involved in CRC remains unknown. In this study, we screened the hotspot mutations of these four genes in 305 CRC samples from Han Chinese by direct sequencing. mRNA expression levels of these genes were quantified by quantitative real-time PCR (RT-qPCR) in paired cancerous and paracancerous tissues. Association analyses between mRNA expression levels and different cancerous stages were performed. Except for one patient harboring IDH1 mutation p.I99M, we identified no previously reported hotspot mutations in colorectal cancer tissues. mRNA expression levels of IDH1, DNMT3A, and MYD88, but not IDH2, were significantly decreased in the cancerous tissues comparing with the paired paracancerous normal tissues. Taken together, the hotspot mutations of IDH1, IDH2, DNMT3A, and MYD88 gene were absent in CRC. Aberrant mRNA expression of IDH1, DNMT3A, and MYD88 gene might be actively involved in the development of CRC.

Keywords: DNMT3A; Expression; IDH1; IDH2; MYD88; Mutation.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • DNA (Cytosine-5-)-Methyltransferases* / biosynthesis
  • DNA (Cytosine-5-)-Methyltransferases* / genetics
  • DNA Methyltransferase 3A
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Hep G2 Cells
  • Humans
  • Isocitrate Dehydrogenase* / biosynthesis
  • Isocitrate Dehydrogenase* / genetics
  • Male
  • Mutation*
  • Myeloid Differentiation Factor 88* / biosynthesis
  • Myeloid Differentiation Factor 88* / genetics
  • Neoplasm Proteins* / biosynthesis
  • Neoplasm Proteins* / genetics
  • Real-Time Polymerase Chain Reaction

Substances

  • DNMT3A protein, human
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • Neoplasm Proteins
  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A