Common mutations prevalent in low-grade ovarian cancers

Mutations in the growth regulatory genes BRAF and KRAS appear to be associated with the development of low-grade ovarian cancer but not of aggressive high-grade ovarian cancer, according to a study in the March 19 issue of the Journal of the National Cancer Institute.

Mutations in BRAF and KRAS are present in a variety of human cancers, and mutations in BRAF are especially prevalent in cutaneous melanoma.

To determine the role of these mutations in ovarian cancer, which is one of the most lethal cancers in women, Gad Singer, M.D., Ie-Ming Shih, M.D., Ph.D., and their colleagues from the Johns Hopkins University School of Medicine examined 182 ovarian tumor samples of different types for the presence of three common mutations in BRAF or KRAS.

They examined serous ovarian cancers, which are the most common type of ovarian cancer and include both high-grade tumors and low-grade tumors, and non-serous ovarian cancers, which are less common and include endometrioid carcinomas and clear-cell carcinomas. The authors also looked for BRAF and KRAS mutations in benign precancerous lesions, which are known precursors to low-grade ovarian tumors.

The authors found one of the three mutations in BRAF and KRAS in 15 of 22 (68%) of the invasive low-grade tumors and in 31 of 51 (61%) of the precancerous lesions. None of the tumors contained a mutation in both genes. In contrast, none of the aggressive high-grade ovarian cancers contained a mutation in either gene. Further, the authors detected BRAF mutations in 24% of endometrioid cancers. They point out that no other gene, except for PTEN, has had such a high mutation rate in ovarian endometrioid cancers.

"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 ovarian serous carcinomas develop through independent pathways," the authors say.

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

Contact: Vanessa Wasta, Johns Hopkins Kimmel Cancer Center, 410-955-1287; fax: 410-614-2611, wastava@jhmi.edu

Singer G, Oldt R 3rd, Cohen Y, Wang BG, Sidransky D, Kurman RJ, et al. Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst 2003;95:484–6.

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage.

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