How Epigenetic Alterations Contribute to Inflammation-driven Cancer
Heather O’Hagan, Ph.D.
Indiana University School of Medicine
NIEHS grantees and colleagues reported a mechanism by which epigenetics, which refers to changes in the way genetic information and proteins are expressed without directly changing the sequence of DNA, may be involved in inflammation-induced tumor development. The team found that epigenetic alterations initiated by inflammation and proteins that correct mismatched base pairs after DNA replication may prevent the expression of tumor suppressor genes.
In mice, the researchers observed that the loss of a specific mismatch repair protein, MutS homolog 2, put an end to the epigenetic alterations observed in inflammation-induced tumors. In addition, they found that tumors induced by inflammation had higher methylation at DNA regions associated with tumor suppressor genes compared with tumors not induced by inflammation.
The team reported that genes with increased DNA methylation exhibited reduced expression at time points that coincided with peak levels of DNA damage associated with inflammation. DNA regions with increased methylation were consistent between inflammation-induced tumors from different mice, suggesting a similarity in the genes whose expression is regulated by DNA methylation.
Approximately 25 percent of all cancers are associated with chronic inflammation. According to the authors, understanding these mechanisms may help the scientific community therapeutically target inflammation-induced epigenetic changes and potentially reduce cancer risk in people with chronic inflammatory diseases.
Citation: Maiuri AR, Peng M, Sriramkumar S, Kamplain CM, DeStefano Shields CE, Sears CL, O'Hagan HM. 2017. Mismatch repair proteins initiate epigenetic alterations during inflammation-driven tumorigenesis. Cancer Res 77(13):3467-3478.
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