ABSENCE OF SIGNIFICANT GERM-LINE P53 MUTATIONS IN OVARIAN-CANCER PATIENTS

Germ line mutations of the p53 gene have been described in the Li-Frau neni Cancer Family Syndrome and occur in patients with multifocal glio mas, particularly those with a history of a metachronous cancer or a f amily history of cancer. p53 dysfunction is often associated with ovar ian cancer. Patients with ovarian carcinoma frequently develop synchro nous or metachronous cancers and may have a family history of this or related cancers. Thus, we hypothesized that germ line p53 mutations mi ght be associated with a significant proportion of ovarian cancers. Ge rm line DNA isolated from peripheral leukocytes of 73 patients with ov arian carcinoma was screened for p53 sequence abnormalities utilizing single-strand conformation polymorphism analysis and direct PCR sequen cing techniques. As many as 40% of this cohort of ovarian cancer patie nts from 67 families may represent familial phenotypes. Synchronous an d metachronous cancers occurred in 19% of the cohort. Only two intron- based polymorphisms were found. Neither has been previously reported. One of these, in intron 6, occurred in three unrelated patients all of whom had a history of metachronous breast cancer. A polymorphism in i ntron 10 occurred in a patient with synchronous endometrial cancer. No classic germ line mutations of p53 were found. (C) 1995 Academic Pres s, Inc.