Nowacka-Zawisza Maria, Bryś Magdalena, Hanna Romanowicz-Makowska, Zadrozny Marek, Kulig Andrzej, Krajewska Wanda M
Department of Cytobiochemistry, University of Lódź.
Pol J Pathol. 2006;57(2):83-9.
This study was carried out to evaluate the loss of heterozygosity (LOH) and microsatellite instability (MSI) in breast cancer, in the 12p13.3 and 1p32 chromosomal regions where RAD52 and RAD54 genes are localized. Polymorphic markers D12S98, D12S1698 for RAD52 and D1S209, D1S411 for RAD54 were used. Relationships between LOH and clinicopathological parameters, i.e. tumor type and grade, patient's age, steroid receptors status and lymph node and distal metastases were assessed. For alleles frequency estimation 100 primary breast cancers were tested. DNA isolated from paraffin-embedded tissues and their matched blood samples were analyzed for PCR-based LOH and MSI by fluorescence-based DNA sequencing technology. In analyzed cases LOH was found in 14% and 11% of informative cases for D12S98 and D12S1698 markers, respectively and in 18% and 17% of informative cases for D1S209 and D1S411 markers, respectively. The highest frequency of MSI was identified at loci D12S98 (10%) and D1S209 (11%). Significant correlations between RAD52 and RAD54 regions with concomitant LOH and histological type and progesterone receptor status were observed. In the case of RAD54 further correlations with respect to tumor grade and the presence of distal metastases were noticed.
本研究旨在评估乳腺癌中杂合性缺失（LOH）和微卫星不稳定性（MSI），研究对象为位于12p13.3和1p32染色体区域的RAD52和RAD54基因。使用了针对RAD52的多态性标记D12S98、D12S1698以及针对RAD54的D1S209、D1S411。评估了LOH与临床病理参数之间的关系，即肿瘤类型和分级、患者年龄、类固醇受体状态以及淋巴结和远处转移情况。为了估计等位基因频率，对100例原发性乳腺癌进行了检测。采用基于荧光的DNA测序技术，对从石蜡包埋组织及其匹配的血液样本中分离出的DNA进行基于PCR的LOH和MSI分析。在分析的病例中，D12S98和D12S1698标记的信息性病例中分别有14%和11%发现了LOH，D1S209和D1S411标记的信息性病例中分别有18%和17%发现了LOH。在D12S98（10%）和D1S209（11%）位点发现了最高频率的MSI。观察到RAD52和RAD54区域与伴随的LOH以及组织学类型和孕激素受体状态之间存在显著相关性。对于RAD54，还注意到与肿瘤分级和远处转移的存在有进一步的相关性。
