Researchers have identified several genes that are linked to one of the most lethal forms of uterine cancer, serous endometrial cancer. The researchers describe how three of the genes found in the study are frequently altered in the disease, suggesting that the genes drive the development of tumors. The findings appear in the October 28, 2012 advance online issue of Nature Genetics. The team was led by researchers from the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health. Cancer of the uterine lining, or endometrium, is the most commonly diagnosed gynecological malignancy in the United States. Also called endometrial cancer, it is diagnosed in about 47,000 American women and leads to about 8,000 deaths each year. Each of its three major subtypes — endometrioid, serous, and clear-cell —is caused by a different constellation of genetic alterations and has a different prognosis. Endometrioid tumors make up about 80 percent of diagnosed tumors. Surgery often is a complete cure for women with the endometrioid subtype, because doctors usually diagnose these cases at an early stage. Compared to other subtypes, the 2 to 10 percent of uterine cancers that comprise the serous subtype do not respond well to therapies. The five-year survival rate for serous endometrial cancer is 45 percent, compared to 65 percent for clear-cell and 91 percent for endometrioid subtypes. Serous and clear-cell endometrial tumor subtypes are clinically aggressive and quickly advance beyond the uterus. "Serous endometrial tumors can account for as much as 39 percent of deaths from endometrial cancer," said Daphne W. Bell, Ph.D., an NHGRI investigator and the paper's senior author. Dr. Bell heads the Reproductive Cancer Genetics Section of NHGRI's Cancer Genetics Branch.
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