Novel complex genomic rearrangement of the BRCA1 gene

Initial BRCA1 and BRCA2 analyses conducted in breast and ovarian cancer families were focused on identification of mutations in coding sequences and splicing sites of the genes. Large genomic rearrangements as well as mutations in promoter or untranslated regions have been missed by standard detection strategies. Nevertheless, in Western countries, a detailed study of families with strong linkage to BRCA1 identified large genomic deletions and rearrangements in this gene as early as 1997. To date, no such gene alteration has been described in Central and Eastern European populations. In our study of BRCA1/2 genes in the Czech population, we have detected a complex genomic rearrangement in BRCA1 using RNA-based analysis for mutation screening. This rearrangement involves exons 21 and 22 and results in a protein product lacking BRCT domain important for its function.