Testing for the Jewish BRCA founder mutations in archived tissue

Abstract

Testing archived tissue for specific BRCA mutations is feasible and thus can be used to attempt to clarify genetic susceptibility to breast and ovarian cancer. This report will review our experience with 3 Ashkenazi Jewish women at increased risk for breast and ovarian cancer based on family history, and whose affected relatives were deceased. Case #1: JB is a 65 year old woman whose daughter died of ovarian cancer at age 42. Case #2: GG is a 43 year old woman whose sister had bilateral breast cancer at age 41 and 46, and whose mother had ovarian cancer at age 50 and breast cancer at age 55. Case #3: DW is a 47 year old woman whose mother, maternal aunt and maternal grandmother each died of ovanan cancer. Each of our patients underwent genetic counseling followed by testing of the three Jewish BRCA founder mutations, and all had normal results. Given their results, they were counseled that the probability they had an inherited susceptibility to breast and ovarian cancer was decreased but could not be excluded. In order to clarify their genetic susceptibility, archived tumor tissue from deceased family members who had breast or ovarian cancer was obtained with consent of the next-of-kin. DNA was isolated from JB's daughter's 2 year old ovarian tumor, from GG's sister's 3 year old breast tumor and from DW's mother's 11 year old ovarian tumor. In each case, the BRCA1 185delAG mutation was identified, consistent with a germline mutation. Therefore, our patients were counseled that it was highly unlikely that they had inherited the cancer susceptibility in their families, which resulted in our recommendations that participation in enhanced preventive strategies, such as prophylactic surgery or chemoprevention, was no longer indicated and there was no contraindication to postmenopausal hormone replacement therapy. In addition, the test results greatly relieved our patients' anxiety for themselves and their offspring. In conclusion, these results demonstrate the value of testing for the Jewish BRCA founder mutations in archived tissue for the purpose of clarifying genetic susceptibility to breast and ovarian cancer in Ashkenazi Jewish individuals. Thus, this strategy should be considered in Ashkenazi Jewish families with breast and/or ovarian cancer when affected relatives are deceased.