New Gene Insights May Explain Ovarian Cancer in Absence of BRCA Mutations

New Gene Insights May Explain Ovarian Cancer in Absence of BRCA Mutations

A gene previously thought to contribute to ovarian cancer by disrupting the well-known BRCA genes, is driving cancer growth independently of the other factors, new research shows.

The discovery is important, as it may explain cases of ovarian and breast cancer where the BRCA genes are normal. New understanding of how the gene, called EMSY, drives cancer development also may lead to novel treatments for women who get ovarian cancer not linked to BRCA.

The study, “The EMSY threonine 207 phospho-site is required for EMSY-driven suppression of DNA damage repair,” was published in the journal Oncotarget.

“Now that we know exactly how changes in EMSY spur cancer cell growth, we can start to design therapies to specifically target that activity and hopefully stop it,” said Douglas Levine, MD, the senior study author, in a press release. Levine is the director of the Division of Gynecologic Oncology at the Perlmutter Cancer Center at the NYU Langone Medical Center.

Up to now, researchers thought that EMSYs part in cancer formation was in suppressing the actions of BRCA2. But the research showed it also could trigger cancer-forming activity when not acting on the known cancer villain.

Just as the BRCA genes, EMSY codes for a protein involved in the repair of DNA. When EMSY becomes abnormally active, it blocks the repair processes. This causes the DNA strands in a cell to start accumulating damage, which leads to cancer.

“This work also suggests that treatments that work for patients with BRCA1 or BRCA2 mutations might also be effective against EMSY-driven cancers because the disease mechanism is similar,” says first study author Petar Jelinic, PhD, a research assistant professor at NYU Langone. “The best way to go rapidly from bench to bedside is to find new ways to use existing treatments.”

The team also identified two key steps in the abnormal function of EMSY. First, the gene became abnormally active, producing more protein than normal. Then, the team found an enzyme places a chemical tag at a specific site in the protein, but only when there is too much of it. Together, these steps turn EMSY into an effective DNA repair suppressor.