Screening for germline rearrangements in BRCA1 and BRCA2in Norwegian families with breast or breast/ovarian cancer

Standard PCR-based mutation detection strategies performed on the BRCA1 and BRCA2 genes of breast and ovarian cancer families are mostly aimed at identifying changes in the coding sequences and in the donor-acceptor splice sites. Hence, mutations in the promoter and the untranslated regions, and large rearrangements, are not detected by these methods. To assess the importance of BRCA1 and BRCA2 alterations that are neglected by standard screening methods, we monitored germline rearrangements in these genes using 'multiplex ligation-dependent probe amplification' technology [1]. One hundred and seventy-nine Norwegian breast and ovarian cancer families were screened for rearrangements in BRCA1 while 97 families were tested for aberrations in BRCA2. Whereas no rearrangements were detected in BRCA2, four distinct deletions were found in BRCA1. Those deletions originating by Alu-mediated homologous recombination include: exons 1–13, exons 3–16, exons 8–13 and exon 23, respectively. The large 23.8 kb deletion excluding exons 8–13 in BRCA1 has been found both in the French and British breast cancer population [2–4]. The deletions of exons 1–13, exons 3–16 and exon 23 have not been previously reported.