De Brakeleer Sylvia, Bogdani Marika, De Grève Jacques, Decock Julie, Sermijn Erica, Bonduelle Maryse, Goelen Guido, Teugels Erik
Laboratory of Molecular Oncology, Department of Medical Oncology, UZ Brussel, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
Mutat Res. 2007 Jun 1;619(1-2):104-12. doi: 10.1016/j.mrfmmm.2007.02.031. Epub 2007 Mar 12.
Enhanced genomic instability has been recently reported in normal cells derived from BRCA1/2 mutation carriers when placed in vitro in non-physiological stress conditions. We present here original data which help to explain the observed genomic instability. Leucocytes from BRCA1/2 mutation carriers, sporadic breast cancer patients and controls were prepared for BRCA1 immunocytochemistry. We show that BRCA1 containing nuclear dot like structures are detectable in about 80% of the leucocytes from controls and sporadic breast cancer patients, but are absent in the majority of normal cells from BRCA1 as well as BRCA2 mutation carriers (also in their normal breast cells). Our results thus indicate that the genomic instability observed in normal cells from BRCA1 and BRCA2 mutation carriers is associated with a down-regulation of nuclear BRCA1 protein accumulation in the dot like structures. These results suggest in addition that immunocytochemical or alternative molecular screening strategies might help to identify women with a high risk for breast (ovarian) cancer even when the underlying genetic defect remains undetectable.
最近有报道称，当置于体外非生理应激条件下时，来自BRCA1/2突变携带者的正常细胞会出现增强的基因组不稳定性。我们在此展示的原始数据有助于解释所观察到的基因组不稳定性。对来自BRCA1/2突变携带者、散发性乳腺癌患者和对照者的白细胞进行BRCA1免疫细胞化学检测。我们发现，在对照者和散发性乳腺癌患者约80%的白细胞中可检测到含有BRCA1的核点状结构，但在BRCA1以及BRCA2突变携带者的大多数正常细胞（包括其正常乳腺细胞）中却不存在。因此，我们的结果表明，在BRCA1和BRCA2突变携带者的正常细胞中观察到的基因组不稳定性与核点状结构中核BRCA1蛋白积累的下调有关。此外，这些结果还表明，免疫细胞化学或其他分子筛查策略可能有助于识别即使潜在基因缺陷仍无法检测到但患乳腺癌（卵巢癌）风险较高的女性。
