New Genetic Mutation Linked to Ovarian Cancer

BY Lea Winerman  September 8, 2010 at 6:42 PM EDT

A genetic mutation linked to one of the most aggressive forms of ovarian cancer may provide clues for new research into treatments and diagnostic tests for the deadly disease, as well as new insight into how other cancers develop.

Two research teams working separately published complementary studies Wednesday. In a study published in the journal Science, researchers at the Johns Hopkins Kimmel Cancer Center found that a mutation in a gene called ARID1A was present in 57 percent of all clear-cell ovarian cancer tumors. Clear-cell carcinomas are one of several types of ovarian cancer. They represent only about 12 percent of all ovarian cancers in the United States, but are particularly aggressive and hard to treat.

Working separately and using a slightly different method, researchers at the University of British Columbia found that an ARID1A mutation was present in 46 percent of clear-cell carcinomas and in 30 percent of endometrioid carcinomas, a more common type of ovarian cancer. That research was published in the New England Journal of Medicine Wednesday.

“The most exciting thing is to have two papers coming out at once,” said David Huntsman of the University of British Columbia, one of the authors of the NEJM study. “That may excite the community to study ARID1A.”

Only 20 percent of ovarian cancers are found before the cancer has spread, according to the Mayo clinic.

The new studies suggest that ARID1a could be a tumor suppressor gene, like the breast cancer gene BRCA, that when mutated can allow tumors to grow. In the case of the ARID1 gene, the gene encodes for a protein that compresses DNA to make it fit inside cells. The way it fits allows certain areas of DNA to be exposed and “read,” turning other genes on or off. When ARID1A gene is mutated, the wrong genes could be turned on or off.

“One of the things we would like to do is find out which genes specifically are the ones that the mutation of ARID1A affects the regulation of,” says Nickolas Papadopoulos Ph.D., an oncologist at the Johns Hopkins Kimmel Cancer Center and one of the authors of the Science study. “Those are the ones we could target for therapeutic research.”

Researchers also hope the finding could lead to new tests for early detection of ovarian cancer, which is often not detected until it has spread to other parts of the body. Only 20 percent of ovarian cancers are found before the cancer has spread, according to the Mayo clinic.