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Gene Mutations May Be Behind Some Ovarian Cancers

Common mutations associated with low-grade forms of disease

TUESDAY, March 18, 2003 (HealthDayNews) -- Mutations in the BRAF and KRAS growth regulatory genes are associated with development of low-grade ovarian cancer, but not with aggressive high-grade ovarian cancer.

Johns Hopkins University School of Medicine researchers examined 182 ovarian tumor samples of different types to search for the presence of three common mutations in BRAF or KRAS. Their work appears in the March 19 issue of the Journal of the National Cancer Institute.

They examined serous ovarian cancers and non-serous ovarian cancers. Serous ovarian cancers are the most common form of ovarian cancer and include both high-grade and low-grade tumors. Non-serous ovarian cancers are less common and include endometrioid carcinomas and clear-cell carcinomas.

The researchers also examined the tumor samples for BRAF and KRAS mutations in benign precancerous lesions, known precursors to low-grade ovarian tumors.

The study found one of the three BRAF and KRAS mutations in 15 of 22 (68 percent) of the invasive low-grade tumors and in 31 of 51 (61 percent) of the precancerous lesions. None of the tumors contained a mutation in both genes.

There were BRAF mutations in 24 percent of endometrioid cancers.

None of the aggressive high-grade tumors contained a mutation the BRAF or KRAS genes.

"The apparent restriction of these BRAF and KRAS mutations to low-grade serous ovarian carcinoma and its precursors suggest that low-grade and high-grade serous carcinomas develop through independent pathways," the researchers write.

Low-grade serous carcinomas generally do not respond well to conventional chemotherapy. Blocking KRAS-BRAF signaling may offer more effective therapy for low-grade serous carcinomas, the authors conclude.

More information

Here's where you can learn more about ovarian cancer.

SOURCE: Journal of the National Cancer Institute, news release, March 18, 2003
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