Large genomic rearrangements in BRCA1 and BRCA2 genes in breast and ovarian cancer families in Poland

Abstract

Mutations in the BRCA1 and BRCA2 genes predispose women to breast and ovarian cancer. The large majority of the alterations identified in these genes are point mutations and small insertion/deletion. However, an increasing number of large genomic rearrangements (LGRs) are being identified, especially in BRCA1. To date just a few large genomic rearrangements of BRCA1 gene have been reported in Poland. Technical limitations of conventional PCR-based methods are cause that gross rearrangements can be overlooked. It has been suggested that about 30% of mutations in the BRCA1 gene are missed by standard mutation detection methods. We screened for LGRs in BRCA1 and BRCA2 genes by Multiplex Ligation-dependent Probe Amplification (MLPA) in 200 unrelated patients with strong family history of breast and/or ovarian cancer negative for BRCA1 Polish founder mutation. We identified 3 different LGRs in BRCA1 gene. No large LGRs were detected in BRCA2 genes.