Buffone Amelia, Capalbo Carlo, Ricevuto Enrico, Sidoni Tina, Ottini Laura, Falchetti Mario, Cortesi Enrico, Marchetti Paolo, Scambia Giovanni, Tomao Silverio, Rinaldi Christian, Zani Massimo, Ferraro Sergio, Frati Luigi, Screpanti Isabella, Gulino Alberto, Giannini Giuseppe
Department of Experimental Medicine, University La Sapienza, Policlinico Umberto I, Viale Regina Elena, 324, Rome 00161, Italy.
Breast Cancer Res Treat. 2007 Dec;106(2):289-96. doi: 10.1007/s10549-007-9499-6. Epub 2007 Feb 28.
Germline point mutations in BRCA1 and BRCA2 genes account for about 30% of the inherited breast and ovarian cancers. Germline genomic rearrangements have been found in both BRCA1 and BRCA2 genes, but the extent to which these alterations might contribute to increasing the actual mutation detection rate is still debated. Here we screened a cohort of 112 consecutive Italian families at moderate-to-high risk for breast and/or ovarian cancer for BRCA1 and BRCA2 point mutations and genomic rearrangements. Of the 83 point mutation negative probands, two (2.4%) showed BRCA1 rearrangements, accounting for 10.5% of the BRCA1 mutations. BRCA1 del18-19 has been previously described in another Italian family, while the molecular characterization of the BRCA1 del23-24 is given here for the first time. Conversely, we failed to identify any BRCA2 rearrangements even in the hereditary breast cancer families, where we detected an higher prevalence of BRCA2 compared to BRCA1 point mutations. Our results support the idea that search for BRCA1 rearrangements should be included in the genetic screening of even moderate risk breast/ovarian cancer families. In contrast, they suggest BRCA2 rearrangements might be very rare out of the high risk families including a male breast cancer.
BRCA1和BRCA2基因的种系点突变约占遗传性乳腺癌和卵巢癌的30%。在BRCA1和BRCA2基因中均发现了种系基因组重排，但这些改变在多大程度上可能有助于提高实际突变检测率仍存在争议。在此，我们对112个连续的意大利中高风险乳腺癌和/或卵巢癌家族进行了BRCA1和BRCA2点突变及基因组重排的筛查。在83名点突变阴性的先证者中，有两名（2.4%）显示出BRCA1重排，占BRCA1突变的10.5%。BRCA1 del18-19先前已在另一个意大利家族中被描述，而BRCA1 del23-24的分子特征在此首次给出。相反，即使在遗传性乳腺癌家族中，我们也未能鉴定出任何BRCA2重排，在这些家族中，我们检测到BRCA2点突变的患病率高于BRCA1。我们的结果支持这样一种观点，即即使在中度风险的乳腺癌/卵巢癌家族的基因筛查中也应包括对BRCA1重排的检测。相比之下，结果表明在包括男性乳腺癌的高风险家族之外，BRCA2重排可能非常罕见。
