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Updated: Jul 19, 2025

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer

Published on: September 18, 2020

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Integrative multi-omic cancer profiling reveals DNA methylation patterns associated with therapeutic vulnerability

Wen-Wei Liang1, Rita Jui-Hsien Lu1, Reyka G Jayasinghe1

  • 1Department of Medicine, Washington University in St. Louis, St. Louis, MO 631110, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.

Cancer Cell
|August 15, 2023
PubMed

Insights

This study reveals how DNA methylation changes drive cancer development across multiple tumor types. Aberrant methylation patterns impact gene expression, cellular identity, and immune response, offering new insights into tumor epigenetics.

Area of Science:

  • Oncology
  • Epigenetics
  • Genomics

Background:

  • DNA methylation is crucial for cellular identity but often altered in cancer.
  • Tumor development involves complex interactions between DNA methylation and other genetic changes.

Purpose of the Study:

  • To create a Pan-Cancer catalog of aberrant DNA methylation.
  • To identify epigenetic drivers linked to gene expression and protein changes.
  • To understand the role of DNA methylation in tumor phenotypes and cell-of-origin.

Main Methods:

  • Multi-omic profiling of 687 tumors and adjacent tissues.
  • Analysis of kidney, brain, pancreas, lung, head and neck, and endometrial cancers.
  • Correlation of methylation data with RNA and protein abundance.

Main Results:

  • Identified lineage-specific epigenetic drivers, such as hypomethylated FGFR2 in endometrial cancer.
  • Found hypermethylated STAT5A linked to gene downregulation and immune cell depletion in squamous tumors.
  • Demonstrated that methylation subtypes correlate with cell-of-origin, heterogeneity, and tumor phenotypes.

Conclusions:

  • DNA methylation events can act as cis-acting drivers of transcriptional and translational changes.
  • Epigenetic regulation of genes like STAT5A may act as a switch for tumor immunosuppression.
  • Understanding the tumor epigenetic landscape, including cell-of-origin influences, is vital for cancer research.

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