Zikan Michal, Pohlreich Petr, Stribrna Jana, Kleibl Zdenek, Cibula David
Department of Biochemistry and Experimental Oncology, First Medical School of Charles University, U Nemocnice 5, 128 00, Prague, Czech Republic.
Mutat Res. 2008 Jan 1;637(1-2):205-8. doi: 10.1016/j.mrfmmm.2007.08.002. Epub 2007 Aug 7.
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.
最初在乳腺癌和卵巢癌家族中进行的BRCA1和BRCA2分析主要集中于识别这些基因编码序列和剪接位点中的突变。标准检测策略遗漏了大片段基因组重排以及启动子或非翻译区的突变。然而，在西方国家，早在1997年对与BRCA1有强连锁关系的家族进行的一项详细研究就已识别出该基因中的大片段基因组缺失和重排。迄今为止，中东欧人群中尚未描述过此类基因改变。在我们对捷克人群BRCA1/2基因的研究中，我们通过基于RNA的突变筛查分析检测到BRCA1中存在一种复杂的基因组重排。这种重排涉及外显子21和22，并导致产生一种缺乏对其功能至关重要的BRCT结构域的蛋白质产物。
