BRCA1 germline mutations in women with uterine serous papillary carcinoma

Objective: To determine the possible effects and incidence of BRCA1 and BRC A2 germline mutations in uterine serous papillary carcinoma. Methods: We screened DNA from 12 women with uterine serous papillary carcin oma for BRCA1 and BRCA2 germline mutations common in the Jewish population (BRCA1-185delAG and 5382insC, BRCA2-6174delT). In women with germline mutat ions, tumor DNA was screened for loss of heterozygosity at the appropriate loci. Results: Nine women were of Jewish Ashkenazi origin and three were non-Ashk enazi. Two of nine Ashkenazi women were carriers of germline mutations: one 185delAG mutation and one 5382insC mutation. Five women had histories of b reast carcinoma before diagnosis of uterine serous papillary carcinoma. Fam ily histories of seven women had at least one first-degree relative with ma lignant disease. Of those, four had at least one first-degree relative with breast, ovarian, or colon carcinoma. Both carriers had strong family histo ries of breast-ovarian carcinoma. Loss of heterozygosity analysis found los s of the wild-type BRCA1 allele in the primary uterine tumors. Conclusion: BRCA1 germline mutations were observed in two of nine of the wo men in this series. The loss of heterozygosity in the tumor tissue of the c arriers, coupled with the high frequency of family and patient histories of breast or ovarian malignancies, suggest that uterine serous papillary carc inoma might be a manifestation of familial breast-ovarian cancer. (Obstet G ynecol 2000;96:28-32. (C) 2000 by The American College of Obstetricians and Gynecologists.).