OCT 20, 2019 4:53 PM PDT

Altered DNA methylation controls genes in cancer

New research published in the journal Genome Biology provides new information on genomic structural variation via DNA methylation and its connection to gene control in human cancers. The research was headed by researchers at Baylor College of Medicine.

DNA methylation refers to the process in which methyl groups are added to a DNA molecule. The occurrence of this methylation can change the activity of a DNA segment without actually changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. It is in this context that methylation becomes of interest to cancer researchers.

"Genomic structural variations occur when a piece of DNA that is in one part of the genome is moved to another part of the genome, which shows up as a break point in the sequence. Therefore, when sequencing a DNA segment, one may find two pieces of DNA from other regions fused together, which disrupts the genetic instructions encoded in DNA," said corresponding author Dr. Chad Creighton, who is an associate professor of medicine and co-director of Cancer Bioinformatics of the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine.

Creighton and his fellow researchers used data from whole-genome sequencing, gene expression and DNA methylation from over 1,400 human cancers in the Cancer Genome Atlas and the Pancancer Analysis of Whole Genomes. The large dataset available to the researchers helped them analyze the impacts of genomic structural variation and identify new genes that are connected to human cancers.

The researchers observed that genomic structural variations did, in fact, have a significant effect on changes in DNA methylation in many of the cancers. "Methylation changes were happening in a non-random way across multiple cancer types," Creighton commented. "Some of these genes were known before to be linked to cancer, but we also identified genes that were not previously associated with this condition. Some genes may be directly involved in the disease, others might be 'passengers.'"

Genomic structural variations  have a significant effect on changes in DNA methylation in many cancers. Photo: Pixabay

Another noteworthy conclusion from the study was that the researchers found that this structural variability across cancers changed depending on the type of cancer. For instance, certain cancers were altered structurally a lot, while other cancers were barely altered at all. This information provides a new way to categorize human cancers that had previously been overlooked.

"We think that our study is unique in the sense that we found that structural variation plays a major role not only in introducing mistakes in DNA sequences but also affecting DNA at the epigenetic level," Creighton said. "We propose that the effect of structural variation on DNA methylation is something to consider when looking for the genetic causes of a cancer."

Sources: Genome Biology, Science Daily

About the Author
  • Kathryn is a curious world-traveller interested in the intersection between nature, culture, history, and people. She has worked for environmental education non-profits and is a Spanish/English interpreter.
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