Overexpression of BRCA2 gene in sporadic breast tumours
Overexpression of BRCA2 gene in sporadic breast tumours
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DOI：
10.1038/sj.onc.1202903
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发表时间：
1999-09-16
期刊：
影响因子：
8
通讯作者：
Lidereau, R
中科院分区：
文献类型：
--
作者：
Bièche, I;Noguès, C;Lidereau, R
乳腺癌易感基因BRCA 2在广泛的组织中表达为Il-lib mRNA转录物，其编码参与对DNA损伤的应答的3418个氨基酸的蛋白质。为了更好地获得散发性乳腺癌中BRCA 2表达的分子特征，我们通过RT-PCR在大量的人原发性乳腺肿瘤中定量BRCA 2 mRNA，BRCA 2表达在肿瘤组织中显示出广泛的变化，在14/127（11%）中低表达，在25/127（20%）中过表达，BRCA 2过表达（但不是低表达）与Scarff，Bloom和Richardson（SBR）组织病理学III级显著相关（P=0.007），主要归因于核多态性（P=0.005）和有丝分裂指数（P=0.048），表明BRCA 2基因有助于乳腺肿瘤的增殖率，BRCA 2状态（低表达和/或过表达vs正常表达）与随后的复发无关，并且与无病生存期显著缩短无关。观察到的BRCA 2表达的中断不是由于等位基因丢失，因为后者与我们的肿瘤系列中BRCA 2 mRNA表达的改变无关。总之，这些数据表明BRCA 2基因参与，特别是通过过度表达，在散发性乳腺肿瘤，和乳腺癌中存在另一个重要的肿瘤抑制基因，在13 q12-q13区域。
The breast cancer susceptibility gene BRCA2 is expressed in a wide range of tissues as an Il-lib mRNA transcript that encodes a 3418-amino acid protein involved in the response to DNA damage. To obtain better a molecular characterization of BRCA2 expression in sporadic breast cancer, we quantified BRCA2 mRNA by means of RT- PCR in a large series of human primary breast tumours, BRCA2 expression showed wide variations in tumour tissues, being underexpressed in 14/127 (11%) and overexpressed in 25/127 (20%), BRCA2 overexpression (but not underexpression) correlated significantly with Scarff, Bloom and Richardson (SBR) histopathological grade III (P=0.007) and was mainly attributed to nuclear polymorphism (P=0.005) and mitotic index (P=0.048), suggesting that the BRCA2 gene contributes to the proliferation rate in breast tumours, BRCA2 status (under and/or overexpression versus normal expression) was not associated with subsequent relapse and with significantly shorter disease-free survival. The observed disruption of BRCA2 expression is not due to allelic loss, because the latter did not correlate with altered BRCA2 mRNA expression in our tumour series. Taken together, these data suggest the involvement, especially by overexpression, of the BRCA2 gene in sporadic breast tumours, and the existence of another important tumour-suppressor gene in breast cancer, in the 13q12-q13 region.