Carcinosarcoma of the ovary in a patient with a germline BRCA2 mutation: evidence for monoclonal origin.

Background: Themajority of hereditary breast and ovarian cancers are associated with germline mutations in BRCA1 or BRCA2. While the occurrence of breast carcinoma and epithelial ovarian carcinoma in association with BRCA mutations is firmly established, the etiologic role of these genes in the development of other tumor types is less well documented. Carcinosarcoma of the ovary is an uncommon tumor consisting of both malignant epithelial and malignant mesenchymal components.

Objective: Here we report a patient with an ovarian carcinosarcoma who was found to harbor a germline mutation in BRCA2. We sought to link the BRCA2 mutation to the pathogenesis of this tumor as well as to determine whether both histologic components arose from the same progenitor cell.

Methods: Microdissection and molecular genetic analyses of the carcinomatous and sarcomatous components of this tumor were performed.

Results: Clonal loss of the wild-type BRCA2 allele as well as the same somatic mutation of the TP53 gene was evident in both histologic components.

Conclusions: These data indicate that hereditary ovarian carcinosarcoma may result from a mutation in BRCA2 and that both histologic elements of this tumor arose from the same progenitor cell.