A Northwestern Medicine study discovered that oncogenes contain specific epigenetic markers called broad genic repression domains (BGRDs), according to findings published in Nature Communications.
These epigenetic features could help investigators identify potential therapeutic targets for cancer treatment.
“For patients who don’t express genetic mutations during cancer progression, based on these epigenetics markers, we can find those genes and determine if they are oncogenes or tumor suppressors,” said Qi Cao, PhD, associate professor of Urology, a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and co-senior author of the study.
Oncogenes can transform normal cells into tumor cells through gain-of-function mutations, a type of genetic mutation in which the altered gene possesses a new function or gene expression. However, the epigenetic mechanisms driving that this process have yet to be determined, according to Cao.
For the current study, the investigators analyzed more than 11,500 epigenetic profiles and mutations from 8,000 pairs of tumor cells and normal cells, with each pair from a single sample. Using integrative analysis, the team discovered that BGRDs were decreased in the chromatin of tumor cells and may represent an epigenetic marker for oncogenes.
BGRDs were also found to repress regions of non-coding DNA that regulate the transcription of neighboring genes in tumor cells.
“With these findings, we may also be able to predict potential therapeutic targets for patients,” Cao said.
This work was supported in by the National Institutes of Health grants GM125632, CA207109, and CA208257, the U.S. Department of Defense grants W81XWH-15-1-0639 and W81XWH-17-1-0357, the American Cancer Society grant TBE-128382, and the Prostate Cancer Foundation grant 13YOUN007.