Epigenetic Changes Drive Cancer

An analysis of almost 700 different tumors revealed that DNA methylation drives tumorigenesis just like genetic mutations do.

Written byRebecca Roberts, PhD
| 3 min read
Clumps of pink, yellow, brown, blue, and green dots on a black background.
Register for free to listen to this article
Listen with Speechify
0:00
3:00
Share

DNA mutations in oncogenes and tumor suppressor genes drive tumorigenesis, but epigenetic modifications, such as DNA methylation, take center stage in a new era of cancer research.1 In a study published in Cancer Cell, researchers cast a wide -omics net to capture extensive DNA methylation, transcriptomic, and proteomic data from almost 700 tumors and healthy tissues. 2 Their findings help unravel the complex effects of methylation on tumor development.

“This study really provides the first look at how methylation and epigenetic modification of the DNA eventually have an impact on the protein abundance, and that those proteins are actually driving cancers,” said Li Ding, an expert in cancer genomics at Washington University in St. Louis and author of the paper.

Scientists often use proteomics data in a targeted way in cancer research, for example, to detect biomarkers in blood for specific cancer types.3 Ding and her colleagues wanted to perform a much broader study to identify entirely new factors involved in the onset of cancer. It was no small feat. They simultaneously ran DNA methylation, transcriptomic, and proteomic analyses to investigate more than 10,000 genes and proteins across seven different cancer types. This unbiased approach allowed them to discover previously unknown methylation events that affect protein levels and drive cancer.

See also: "Epigenetic Marks May Cause Brain Tumor Formation"

One finding in particular caught Ding’s attention. Hypomethylation on fibroblast growth factor receptor 2 (FGFR2), a receptor tyrosine kinase (RTK) oncogene, increased transcript and protein abundance and drove cancer activity. Genetic mutations in FGFR2 drive tumorigenesis, particularly in endometrial cancer, but Ding’s evidence shows that epigenetic modifications similarly promote oncogenesis.

“We’re very excited about this because it’s a breakthrough, and it’s very definitive,” Ding remarked. “We also found that [methylation and genetic mutations] are often mutually exclusive. When you have hypomethylation of FGFR2, you often don’t see the mutations, and vice versa.”

Similarly, the team found that epidermal growth factor receptor (EGFR), another RTK oncogene, is also regulated by both genetic and epigenetic drivers. In fact, hypomethylation of EGFR, which corresponded to an increase in EGFR transcripts and protein abundance, was common across multiple cancer types.

Ding and her colleagues found that epigenetic modifications also affect transcription factors, causing far-reaching effects on the larger gene networks that they control. For example, hypermethylation of signal transducer and activator of transcription 5A (STAT5A) correlated with a reduction in both the RNA transcripts and proteins produced by the genes it regulates. The effects of these epigenetic edits extended to the tumor microenvironment, reducing the number of immune cells available to combat tumor growth.

Stephen Baylin, a cancer biologist at Johns Hopkins Medicine who was not involved in the study, said that he was enthusiastic about the results of the paper and Ding’s approach. “I would add that it's really important to stratify these events, not only to establish cancers but premalignancy and how [the tumors] evolved from the parent cells, and drill down on that even more,” Baylin remarked.

See also: "Jumping Genes' Role in Cancer"

According to Ding, the results of the study highlight potential druggable targets. Almost 20 percent of the tumors studied could potentially be treated by targeting methylated genes like EGFR. They also postulated that pharmacological activation of hypermethylated STAT5A signaling could boost the antitumor immune response, increasing inflammation to warm up uninflamed tumors.4

“This will have particular interest for clinicians who are actually developing strategies for treating patients by employing or leveraging the immune system within the tumor,” Ding concluded.

Related Topics

Meet the Author

  • Rebecca Roberts,PhD

    Rebecca Roberts is a science writer and communicator. She earned her PhD in molecular biology from the University of the Sunshine Coast in Australia and completed a two-year postdoctoral fellowship at Lund University in Sweden. Her writing focuses on gene editing technology, cell and gene therapies, and the regulatory space.

    View Full Profile
Share
You might also be interested in...
Loading Next Article...
You might also be interested in...
Loading Next Article...
July Digest 2025
July 2025, Issue 1

What Causes an Earworm?

Memory-enhancing neural networks may also drive involuntary musical loops in the brain.

View this Issue
Accelerating Recombinase Reprogramming with Machine Learning

Accelerating Recombinase Reprogramming with Machine Learning

Genome Modeling and Design: From the Molecular to Genome Scale

Genome Modeling and Design: From the Molecular to Genome Scale

Twist Bio 
Screening 3D Brain Cell Cultures for Drug Discovery

Screening 3D Brain Cell Cultures for Drug Discovery

DNA and pills, conceptual illustration of the relationship between genetics and therapeutic development

Multiplexing PCR Technologies for Biopharmaceutical Research

Thermo Fisher Logo

Products

waters-logo

Waters and BD's Biosciences & Diagnostic Solutions Business to Combine, Creating a Life Science and Diagnostics Leader Focused on Regulated, High-Volume Testing

zymo-research-logo

Zymo Research Partners with Harvard University to Bring the BioFestival to Cambridge, Empowering World-class Research

10x-genomics-logo

10x Genomics and A*STAR Genome Institute of Singapore Launch TISHUMAP Study to Advance AI-Driven Drug Target Discovery

The Scientist Placeholder Image

Sino Biological Sets New Industry Standard with ProPure Endotoxin-Free Proteins made in the USA