BRCA1 GENE-MUTATIONS IN WOMEN WITH PAPILLARY SEROUS CARCINOMA OF THE PERITONEUM

Objective: To compare BRCA1 mutations in papillary serous carcinoma of the peritoneum and papillary serous ovarian carcinoma. Methods: Germl ine DNA from 17 consecutive patients with peritoneal carcinoma was scr eened for mutations in the BRCA1 gene using single-strand conformation polymorphism analysis. Shifted DNA bands were sequenced. Patients wit h germline BRCA1 mutations were screened for allelic loss in tumor DNA at the BRCA1 locus. Results: Two of the 17 patients (11%, 95% confide nce interval 0.07, 0.37) exhibited the 185 delAG germline BRCA1 mutati on described in the Ashkenazi Jewish population. The family history of one patient was notable for a mother and five aunts with breast or ov arian cancer. The other patient had a personal history of breast cance r. Both patients exhibited allelic loss of the normal BRCA1 allele in their tumor. A third patient was found to have a previously undescribe d exon 11 single base pair substitution at nucleotide 1239 (CAG to CAC ) resulting in a missense mutation (Gln to His). The patient had no fa mily or personal history of breast or ovarian cancer, and her tumor di d not exhibit loss of heterozygosity. Conclusion: Germline BRCA1 mutat ions occur in papillary serous carcinoma of the peritoneum with a freq uency comparable to the BRCA1 mutation rate in ovarian cancer. Althoug h the penetrance is unknown, peritoneal carcinoma should be considered a malignancy expressed in the familial breast ovarian cancer syndrome . (Obstet Gynecol 1998;92:596-600. (C) 1998 by The American College of Obstetricians and Gynecologists.).