BRCA1-RELATED BREAST-CANCER IN AUSTRIAN BREAST AND OVARIAN-CANCER FAMILIES - SPECIFIC BRCA1 MUTATIONS AND PATHOLOGICAL CHARACTERISTICS

We identified 17 BRCAl mutations in 86 Austrian breast and ovarian can cer families (20%) that were screened for mutations by denaturing high -performance liquid chromatography (DHPLC) and the protein truncation test (PTT). Eleven distinct mutations were detected, 4 of them (962del 4, 2795del4, 3135del4 and L3376stop) not previously reported in famili es of non-Austrian origin. In addition, 6 rare missense mutations (all ele frequency < 1%) with unknown biological effects were identified. F our mutations occurred more than once in the Austrian population: 2795 del4 (3 times), Cys61 Gly (3 times) 5382insC (2 times) and Q1806stop ( 2 times). Haplotype analysis of the 4 recurrent mutations suggested a common ancestor for each of these. Thirty-four breast cancer cases fro m 17 families with BRCAl mutations were further analyzed. We observed a low median age of onset (39.5 years). Sixty-eight percent of all BRC Al breast cancer cases had negative axillary lymph nodes. This group s howed a significant prevalence of a negative estrogen and progesterone receptor status and stage I tumors compared with an age-related, node -negative control group. The prevalence of grade 111 tumors was margin ally significant. Survival analysis either with a control group matche d for age (within 5 years), grade, histologic subtype and estrogen rec eptor status, or with an age-related, node-negative comparison group, showed no statistical difference. (C) 1998 Wiley-Liss, Inc.