Two Genes Linked to Chemotherapy Resistant Ovarian Cancer

Kathleen Blanchard's picture

Researchers have tied two genes to a deadly ovarian cancer that is generally resistant to chemotherapy. Clear cell ovarian cancer – the most resistant to treatment – has been found by Johns Hopkins scientists to be linked to two genetic mutations. One of the genes normally suppresses cancer cells and the other turns normal cells into tumors if altered.

ARID1A and PPP2R1A Gene Alterations may Play a Significant Role in Ovarian Cancer

In the study, ARID1A, the gene that suppresses cancer was found to be mutated in more than half of ovarian tumors studied. PPP2R1A mutations were found in seven percent of 18,000 protein-encoding genes analyzed, comparing them the normal cells of the same patients.

Twenty mutated genes in clear cell ovarian cancer cells were studied. ARID1 and PPP2R1A were the most common genes mutated in the deadly form of ovarian cancer.

According to Nickolas Papadopoulos, Ph.D., an associate professor of oncology and director of Translational Genetics at the Ludwig Center for Cancer Genetics & Therapeutics at the Johns Hopkins Kimmel Cancer Center, the new findings “may provide opportunities for developing new biomarkers and therapies that target those genes.”

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Until now there was no known association between clear cell ovarian cancer and the two genes. Papadopoulos likens prevalent gene alterations to mountains, compared to those that are less common, saying, “ARID1A is one of the biggest mountains found in recent years”.

Victor Velculescu, M.D., Ph.D., associate professor of oncology at the Johns Hopkins Kimmel Cancer Center explains, “The mutations in ARID1A provide an important new link between genetic and epigenetic mechanisms in human cancer and may help identify epigenetic changes which can be targeted with therapies.”

Epigenetics refers to changes that occur in genes outside of the normal cellular structure. ARID1A is part of a chromatin remodeling complex, that when rearranged, exposes DNA. The result is that genes abnormally get switched on and off. Siân Jones, Ph.D., research associate at the Johns Hopkins Kimmel Cancer Center says, “This gene may play a significant role in this type of cancer.”

The next step is to find genes whose chromatin is specifically influenced by ARID1A inactivation. Clear cell ovarian cancer affects women age 40 to 80. Finding the two gene mutations for the deadly form of ovarian cancer could lead to targeted gene therapy to treat the disease that is generally resistant to chemotherapeutic agents.

Science DOI: 10.1126/science.1196333