Agata Simona, Viel Alessandra, Della Puppa Lara, Cortesi Laura, Fersini Giusi, Callegaro Monia, Dalla Palma Maurizia, Dolcetti Riccardo, Federico Massimo, Venuta Salvatore, Miolo Gianmaria, D'Andrea Emma, Montagna Marco
Department of Oncology and Surgical Sciences, Oncology Section, University of Padua, Padua, Italy.
Genes Chromosomes Cancer. 2006 Sep;45(9):791-7. doi: 10.1002/gcc.20342.
The presence of genomic rearrangements of the BRCA1 gene in breast and/or ovarian cancer families has been intensively investigated in patients from various countries over the last years. A number of different rearrangements have been reported by several studies that clearly document the involvement of this mutation type in genetic predisposition to breast and ovarian cancer. Population-specific studies are now needed to evaluate the prevalence of genomic rearrangements before deciding whether to include ad hoc screening procedures into standard diagnostic mutation detection approaches. Indeed, the vast majority of the studies have been performed on small, highly selected, sample sets because of the limitations imposed by the laborious technical approaches. Moreover, prevalence figures are likely to differ across different countries according to the ethnic origin of each specific population. Here we analyze a large cohort of 653 Italian probands, negative for BRCA1 and BRCA2 point mutations, gathered from four National Institutions. We report the identification of BRCA1 genomic rearrangements in 12 independent families. Noteworthy, half of the probands carry mutations that recur in more than one Italian family. Considering the whole spectrum of Italian BRCA1 gene rearrangements identified thus far in consecutive patients, we estimate that alterations of this type account for 19% (95% CI: 0.11 < 0.19 < 0.28) of the BRCA1 mutation positive families. We conclude that the search for major genomic rearrangements is essential for an accurate and comprehensive BRCA1 mutation detection strategy in Italy.
在过去几年中，来自各个国家的患者对乳腺癌和/或卵巢癌家族中BRCA1基因的基因组重排情况进行了深入研究。多项研究报告了一些不同的重排情况，这些研究清楚地证明了这种突变类型与乳腺癌和卵巢癌的遗传易感性有关。现在需要进行针对特定人群的研究，以评估基因组重排的患病率，然后再决定是否将专门的筛查程序纳入标准诊断性突变检测方法中。事实上，由于繁琐的技术方法带来的限制，绝大多数研究都是在小样本、高度选择的样本集上进行的。此外，根据每个特定人群的种族起源，不同国家的患病率数据可能会有所不同。在这里，我们分析了来自四个国家机构的653名意大利先证者组成的大型队列，这些先证者BRCA1和BRCA2点突变为阴性。我们报告在12个独立家族中鉴定出BRCA1基因组重排。值得注意的是，一半的先证者携带的突变在不止一个意大利家族中出现。考虑到迄今为止在连续患者中鉴定出的意大利BRCA1基因重排的全貌，我们估计这种类型的改变占BRCA1突变阳性家族的19%（95%置信区间：0.11 < 0.19 < 0.28）。我们得出结论，在意大利，寻找主要的基因组重排对于准确和全面的BRCA1突变检测策略至关重要。
