Gliomas are incurable brain tumors. Researchers are trying to unlock the mysteries of how they originate from normal cells, which may lead to better treatments. A new study published in the journal Cell centers on epigenetic rather than genetic changes that drive normal cells to form tumors. The work reveals the precise genes that are regulated epigenetically and lead to cancer.
Genes make us who we are in many ways and are central to defining our health. Cancer is often viewed as a disease caused by changes in our genes, thus our DNA. Epigenetics is the study of how behavior, environment or metabolic changes can cause alterations to the way genes work. Unlike genetic changes, epigenetic changes do not change one’s DNA, and they can be reversed.
“We used tumor samples and mouse modeling to discover and functionally demonstrate the role of epigenetic alterations in gliomas,” said Gilbert J. Rahme, first author and assistant professor in the Department of Pharmacological Sciences at the Renaissance School of Medicine, and formerly a postdoctoral fellow at the Dana-Farber Cancer Institute in Boston. “By doing this, we discovered genes regulated epigenetically in gliomas, including potent tumor suppressor genes and oncogenes, that drive the tumor growth.”
In the paper, titled “Modeling epigenetic lesions that cause gliomas,” the research team show in the model that epigenetic alterations of tumor suppressor and oncogenes collaborate together to drive the genesis of this brain tumor.
The authors explain that “epigenetic activation of a growth factor receptor, the platelet-derived growth factor receptor A (PDGFRA) occurs by epigenetic disruption of insulator sites, which act as stop signs in the genome to prevent aberrant activation of genes. The activation of PDGFRA works in concert with the epigenetic silencing of the tumor suppressor Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) to transform a specific cell type in the brain, the oligodendrocyte progenitor cell (OPC), driving the formation of brain tumors.”
Rahme says the next step is to test whether therapies that can reverse the epigenetic changes observed in brain tumors can be helpful as a treatment.