Fox Chase Cancer Center researchers identify novel target for detecting ovarian cancer in blood

PHILADELPHIA (September 10, 2004)--Fox Chase Cancer Center researchers have found a new way to detect ovarian cancer in the blood. Reported in the Sept. 15, 2004, issue of Cancer Research, the new method targets hypermethylation--one mechanism used by cancer cells to turn off genes that protect against tumor development.

When these tumor-suppressor genes are inactivated by hypermethylation, they cannot do their job, which then allows cancer cells to develop. This research marks the first time hypermethylation has been examined for the detection of ovarian cancer.

Fox Chase molecular biologist Paul Cairns, Ph.D., and his colleagues tested for hypermethylation of BRCA1 and RASSF1A, two genes strongly associated with ovarian cancer.

"In normal cells, BRCA1 and RASSF1A are unmethylated, meaning they are able to do their job. We found these genes to be frequently hypermethylated in the blood and peritoneal fluid from patients with ovarian cancer," explained Cairns.

Tumor samples, preoperative blood and peritoneal fluid DNA were obtained and matched from 50 patients with ovarian or primary peritoneal cancer. The blood from 20 healthy age-matched women, normal ovary tissue from 10 women, and tissue, blood and peritoneal fluid from 10 women with benign ovarian cysts were used for controls.

Thirty-four of the 50 tumors (68 percent) showed hypermethylation of one or both genes. The remaining 16 tumor samples, which did not show hypermethylation for RASSF1A or BRCA1, had hypermethylated forms of other tumor-suppressor genes: APC, p14, p16 and DAP (death-associated protein-kinases), which provided a target for screening.

An identical pattern of gene hypermethylation was found in the matched blood DNA from 41 of 50 patients (82 percent sensitivity), including 13 of 17 cases of stage I disease. No hypermethylation was observed in the non-cancerous tissue, peritoneal fluid or blood from control samples (100 percent specifici

Contact: Karen Carter Mallet
Fox Chase Cancer Center

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