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Updated: Dec 21, 2025

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

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[Functional Hypermethylation of ALDH1L1, PLCL2, and PPP2R3A in Colon Cancer]

A A Dmitriev1,2, A D Beniaminov1, N V Melnikova1

  • 1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.

Molekuliarnaia Biologiia
|May 12, 2020
PubMed

Insights

DNA hypermethylation frequently silences tumor suppressor genes in colon cancer. ALDH1L1, PLCL2, and PPP2R3A show decreased expression due to promoter hypermethylation, indicating their role in colon cancer suppression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Tumor suppressor gene downregulation is critical in cancer development.
  • DNA hypermethylation and mutations are key mechanisms driving this process.
  • Understanding these mechanisms in colon cancer is crucial for therapeutic strategies.

Purpose of the Study:

  • To identify genes downregulated by hypermethylation in colon cancer.
  • To investigate the suppressor role of specific genes in colon tumorigenesis.
  • To establish the functional significance of promoter hypermethylation in colon cancer.

Main Methods:

  • NotI-microarray analysis of 180 NotI sites in 188 genes from human chromosome 3 in paired colon samples.
  • Analysis of gene expression and promoter methylation data from The Cancer Genome Atlas (TCGA).
  • Quantitative PCR validation of gene expression in 30 paired colon samples.

Main Results:

  • Frequent promoter hypermethylation and/or deletions were detected in 20 genes.
  • Three genes (ALDH1L1, PLCL2, PPP2R3A) showed decreased expression correlated with promoter hypermethylation.
  • Quantitative PCR confirmed significant mRNA level decrease (5-9-fold) in over 60% of tumor samples for these three genes.

Conclusions:

  • ALDH1L1, PLCL2, and PPP2R3A function as tumor suppressors in colon cancer.
  • Promoter hypermethylation is a significant mechanism for the downregulation of these suppressor genes.
  • These findings highlight potential therapeutic targets for colon cancer intervention.
Keywords:
DNA methylationcolon cancertumor suppressor genes

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