Expression and promoter methylation status of hMLH1, MGMT, APC, and CDH1 genes in patients with colon adenocarcinoma

Exp Biol Med (Maywood). 2015 Dec;240(12):1599-605. doi: 10.1177/1535370215583800. Epub 2015 Apr 23.

Abstract

Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. CRC development is the result of genetic and epigenetic alterations accumulation in the epithelial cells of colon mucosa. In the present study, DNA methylation, an epigenetic event, was evaluated in tumoral and matching normal epithelium in a cohort of 61 CRC patients. The results confirmed and expanded knowledge for the tumor suppressor genes hMLH1, MGMT, APC, and CDH1. Promoter methylation was observed for all the examined genes in different percentage. A total of 71% and 10% of the examined cases were found to be methylated in two or more and in all genes, respectively. mRNA and protein levels were also evaluated. Promoter methylation of hMLH1, MGMT, APC, and CDH1 genes was present at the early stages of tumor's formation and it could also be detected in the normal mucosa. Correlations of the methylated genes with patient's age and tumor's clinicopathological characteristics were also observed. Our findings suggest that DNA methylation is a useful marker for tumor progression monitoring and that promoter methylation in certain genes is associated with more advanced tumor stage, poor differentiation, and metastasis.

Keywords: Colon cancer; CpG islands; epigenetics; methylation; methylation-specific PCR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism*
  • Aged
  • Antigens, CD
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Colon / pathology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • DNA Modification Methylases / metabolism*
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MutL Protein Homolog 1
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • APC protein, human
  • Adaptor Proteins, Signal Transducing
  • Adenomatous Polyposis Coli Protein
  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • MLH1 protein, human
  • Nuclear Proteins
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • MutL Protein Homolog 1
  • DNA Repair Enzymes