Nowacka-Zawisza Maria, Bryś Magdalena, Romanowicz-Makowska Hanna, Kulig Andrzej, Krajewska Wanda M
Department of Cytobiochemistry, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland.
Cancer Detect Prev. 2008;32(2):144-8. doi: 10.1016/j.cdp.2008.06.005. Epub 2008 Jul 16.
Loss of heterozygosity (LOH) in the 15q14-21 and 13q12-13 regions can contribute to the inactivation of RAD51 and BRCA2 genes implicated in the pathogenesis of breast cancer. We investigated allelic losses in microsatellites in the RAD51 and BRCA2 regions, and their association with clinicopathological parameters in breast cancer.
The LOH analysis was performed by amplifying DNA by PCR, using D15S118, D15S214, D15S1006 polymorphic markers in the 15q14-21 region and D13S260, D13S290 polymorphic markers in the 13q12-13 region in 36 sporadic breast cancer cases.
LOH in the RAD51 region ranged from 29% to 46% and in the BRCA2 region from 38% to 43% of informative cases. Eleven percent of the breast cancer cases displayed LOH for at least one studied marker in the RAD51 region exclusively. On the other hand, 44% of cases manifested statistically significant LOH for at least one microsatellite marker concomitantly in the RAD51 and BRCA2 regions. LOH in the RAD51 region similarly as in the BRCA2 region appeared to correlate with steroid receptors content and lymph node status.
The obtained results indicate that alteration in RAD51 region may contribute to the disturbances of DNA repair involving RAD51 and/or BRCA2 penetration and thus enhance the risk of breast cancer development.
15q14 - 21和13q12 - 13区域的杂合性缺失（LOH）可能导致参与乳腺癌发病机制的RAD51和BRCA2基因失活。我们研究了RAD51和BRCA2区域微卫星中的等位基因缺失及其与乳腺癌临床病理参数的关联。
采用聚合酶链反应（PCR）扩增DNA，对36例散发性乳腺癌病例使用15q14 - 21区域的D15S118、D15S214、D15S1006多态性标记以及13q12 - 13区域的D13S260、D13S290多态性标记进行LOH分析。
在有信息的病例中，RAD51区域的LOH范围为29%至46%，BRCA2区域为38%至43%。11%的乳腺癌病例仅在RAD51区域至少有一个研究标记显示LOH。另一方面，44%的病例在RAD51和BRCA2区域同时至少有一个微卫星标记表现出具有统计学意义的LOH。RAD51区域的LOH与BRCA2区域类似，似乎与类固醇受体含量和淋巴结状态相关。
所得结果表明，RAD51区域的改变可能导致涉及RAD51和/或BRCA2渗透的DNA修复紊乱，从而增加乳腺癌发生的风险。
