Department of Genetics, Faculty of Medicine, Wroclaw Medical University, Marcinkowskiego 1, 50-368, Wroclaw, Poland.
Lower Silesian Oncology, Pulmonology and Hematology Center, Hirszfeld Sq. 12, 53-413, Wroclaw, Poland.
Breast Cancer Res Treat. 2024 Dec;208(3):501-510. doi: 10.1007/s10549-024-07441-4. Epub 2024 Jul 30.
Homologous recombination (HR) is a crucial DNA-repair mechanism, and its disruption can lead to the accumulation of mutations that initiate and promote cancer formation. The key HR genes, BRCA1 and BRCA2, are particularly significant as their germline pathogenic variants are associated with a hereditary predisposition to breast and/or ovarian cancer.
The study was performed on 45 FFPE breast cancer tissues obtained from 24 and 21 patients, with and without the germline BRCA1/2 mutation, respectively. The expression of 11 genes: BRCA1, BRCA2, ATM, BARD1, FANCA, FANCB, FANCI, RAD50, RAD51D, BRIP1, and CHEK2 was assessed using Custom RT2 PCR Array (Qiagen), and results were analysed using R.
Cancer tissues from patients with BRCA1 or BRCA2 germline mutations displayed no significant differences in the expression of the selected HR genes compared to BRCA1 or BRCA2 wild-type cancer tissues. In BRCA1 cancer tissues, BRCA1 expression was significantly higher than in BRCA2 and BRCA wild-type cancer tissues.
In cancer tissues harbouring either BRCA1 or BRCA2 germline mutations, no significant differences in expression were observed at the mRNA level of any tested HR genes, except BRCA1. However, the significant differences observed in BRCA1 expression between germline BRCA1, germline BRCA2 and BRCA1/2 tissues may indicate a compensatory mechanism at the mRNA level to mitigate the loss of BRCA1 function in the cells.
同源重组（HR）是一种至关重要的 DNA 修复机制，其破坏可导致引发和促进癌症形成的突变积累。关键的 HR 基因 BRCA1 和 BRCA2 尤为重要，因为它们的种系致病性变体与乳腺癌和/或卵巢癌的遗传易感性有关。
该研究在 24 名和 21 名分别具有和不具有种系 BRCA1/2 突变的患者的 45 个 FFPE 乳腺癌组织中进行。使用 Custom RT2 PCR Array（Qiagen）评估了 11 个基因：BRCA1、BRCA2、ATM、BARD1、FANCA、FANCB、FANCI、RAD50、RAD51D、BRIP1 和 CHEK2 的表达，并使用 R 进行了分析。
与 BRCA1 或 BRCA2 野生型癌症组织相比，具有 BRCA1 或 BRCA2 种系突变的癌症组织中所选 HR 基因的表达没有显著差异。在 BRCA1 癌症组织中，BRCA1 的表达明显高于 BRCA2 和 BRCA 野生型癌症组织。
在携带 BRCA1 或 BRCA2 种系突变的癌症组织中，除 BRCA1 外，在任何测试的 HR 基因的 mRNA 水平上均未观察到表达的显著差异。然而，在种系 BRCA1、种系 BRCA2 和 BRCA1/2 组织之间观察到的 BRCA1 表达的显著差异可能表明在 mRNA 水平上存在补偿机制，以减轻细胞中 BRCA1 功能的丧失。
