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Release: Nov. 1, 2000

UI researchers report gene a significant predictor of survival for ovarian cancer patients

IOWA CITY, Iowa -- A functionally null p53 gene -- the gene that produces a protein that triggers human cell repair and controls tumor cell growth -- is a significant molecular predictor of survival for patients with ovarian cancer, according to a study by University of Iowa Health Care researchers.

In a study published in the Nov. 1 issue of the journal Cancer, UI researchers report that the median survival for ovarian cancer patients with p53 null mutations was 1.49 years, compared with 3.6 years for ovarian cancer patients with p53 missense mutations.

When functioning normally, the p53 gene produces a protein that controls rapid cell growth and helps chemotherapy work more effectively. Null mutations to the p53 gene leave tumors devoid of the tumor-inhibiting protein; missense mutations are minor alterations that still allow the p53 gene's tumor-suppressing protein to be made.

"We found that the p53 gene was altered or mutated in at least 70 percent of the advanced ovarian cancer cases we analyzed," said Richard Buller, M.D., Ph.D., UI professor of obstetrics and gynecology and the study's principal investigator. "The results further validate that p53 alterations in ovarian cancer are common and therefore are a good target for new therapeutic strategies such as gene replacement."

UI investigators analyzed 171 patients, ages 40 to 70, diagnosed with invasive ovarian cancer and treated at the UI Hospitals and Clinics between 1990 and 1996.

Buller, who directs the gynecologic oncology division in obstetrics and gynecology, said a next step for the researchers is to analyze missense mutations as a group. "We think there are probably missense mutations that are very detrimental while others cause only minimal disruption," he said. "We're working on both molecular and analytic methods to differentiate between the types of missense mutations, to give more accurate prognoses to ovarian cancer patients after they have had surgery."

Buller and his colleagues also are participating in a phase II/III gene replacement trial with researchers from around the world. Sponsored by the Schering Plough Corp, the work involves placing a normal p53 gene back into the cells of ovarian cancer tumors.

"There is a strong rationale for this type of therapy. Early results have shown that gene replacement with chemotherapy may be more effective than chemotherapy alone in treating these tumors," Buller said.

Co-investigators on the UI study were Mark Shahin, M.D., senior fellow in obstetrics and gynecology and lead author of the paper; Jonathon Hughes, M.D., Ph.D., a former UI faculty member now in private practice; and Anil Sood, M.D., assistant professor of obstetrics and gynecology.

University of Iowa Health Care describes the partnership between the UI College of Medicine and the UI Hospitals and Clinics and the patient care, medical education and research programs and services they provide.