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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
07:50

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer

Published on: September 18, 2020

DNA methylation changes in cancer

Minoru Toyota1, Eiichiro Yamamoto

  • 1Department of Biochemistry, Sapporo Medical University, Chuo-ku, Sapporo, Japan.

Progress in Molecular Biology and Translational Science
|April 22, 2011
PubMed

Insights

DNA methylation and histone modifications silence tumor-suppressor genes in cancer. These epigenetic changes, driven by DNA methyltransferases (DNMTs), affect various cancer pathways and can be reversed by DNMT inhibitors.

Area of Science:

  • Epigenetics and Cancer Biology

Background:

  • Epigenetic alterations, including DNA methylation and histone modifications (deacetylation, H3K9/K27 methylation), are crucial in the silencing of tumor-suppressor genes.
  • These epigenetic changes are implicated in various cancer hallmarks such as cell-cycle control, apoptosis, angiogenesis, and immune evasion.

Purpose of the Study:

  • To elucidate the mechanisms driving DNA methylation changes in cancer.
  • To understand the role of DNA methylation in specific cancer subtypes, including those with the CpG island methylator phenotype (CIMP).

Main Methods:

  • Analysis of DNA methylation patterns in cancer genomes.
  • Investigation of the involvement of DNA methyltransferases (DNMTs), inflammation, and viral infections in aberrant DNA methylation.
  • Examination of epigenetic modifications in cancers exhibiting the CpG island methylator phenotype (CIMP).

Main Results:

  • Aberrant DNA methylation, influenced by DNMT activity, inflammation, and viral factors, silences critical tumor-suppressor genes.
  • Cancers with the CpG island methylator phenotype (CIMP) display distinct genetic alterations, including microsatellite instability and BRAF mutations.
  • Hypomethylation of repetitive elements contributes to chromosomal instability in cancer.

Conclusions:

  • DNA methylation is a key epigenetic mechanism driving cancer development and progression by affecting multiple gene functions.
  • The reversibility of DNA methylation offers therapeutic potential, as demonstrated by DNMT inhibitors' ability to restore gene expression.

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