Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Via Sergio Pansini 5, 80131 Napoli, Italy.
CEINGE-Biotecnologie Avanzate, Via G. Salvatore 486, 80145 Napoli, Italy.
Genes (Basel). 2022 Apr 13;13(4):682. doi: 10.3390/genes13040682.
/ are tumor suppressor genes involved in DNA double-strand break repair. They are the most penetrant genes for hereditary breast and ovarian cancers, but pathogenic variants in these two genes can be identified only in a fraction of hereditary cases. Following the diffusion of molecular testing and the availability of specific therapeutic strategies for the management of pathogenic variant carriers, the demand for the analysis of additional predisposing genetic factors has increased. Indeed, there is accumulating evidence regarding the role of other genes, including and Both of them are involved in the same molecular pathway as genes, with being responsible for cell cycle stopping to allow the repair of DNA double-strand breaks and being able to interact with and activate . Thus, their role as additional hereditary cancer predisposing factors is intriguing. Accordingly, guidelines for hereditary cancer risk assessment have been updated to include the criteria for additional genes testing. In this context, we validated a commercially available kit allowing for the simultaneous analysis of , , and . Forty-eight patients, already tested for mutational status, were re-analyzed in the present study. Results comparison showed that the tested method was able to correctly identify all the variants previously detected in the same patients. In particular, all single-nucleotide variants and small indels were correctly identified. Moreover, two copy number variants, included to assess the software's performance in detecting this kind of gene alteration, were also detected. Even if copy number variant estimation still requires confirmation by a molecular technique to avoid false positive results, it is able to reduce the number of patients requiring multiplex ligation probe amplification analysis, positively impacting the test's turnaround time. Finally, since the time and costs of the analysis are similar to those required just for genes, this strategy may be affordable for providing a more comprehensive test for hereditary cancer risk assessment.
抑癌基因参与 DNA 双链断裂修复。它们是遗传性乳腺癌和卵巢癌最具外显性的基因，但这两个基因中的致病变体只能在一部分遗传性病例中识别。随着分子检测的普及以及针对致病性变异携带者的特定治疗策略的出现，对分析其他潜在遗传因素的需求增加了。事实上，越来越多的证据表明其他基因的作用，包括 BRCA1 和 BRCA2。这两个基因都与 BRCA1 基因参与相同的分子途径，其中 BRCA2 负责细胞周期停止以允许修复 DNA 双链断裂，而能够与 BRCA1 和激活 RAD51。因此，它们作为额外的遗传性癌症易感因素的作用令人着迷。因此，遗传性癌症风险评估指南已更新，以包括其他基因检测的标准。在这种情况下，我们验证了一种商业上可用于同时分析 BRCA1、BRCA2、PALB2 和 RAD51 的试剂盒。在本研究中，对 48 名已经检测到 BRCA1 突变状态的患者进行了重新分析。结果比较表明，所测试的方法能够正确识别以前在同一患者中检测到的所有变体。特别是，所有单核苷酸变体和小插入缺失都被正确识别。此外，还检测到两种拷贝数变异，包括评估软件检测这种基因改变的性能，即使拷贝数变异估计仍然需要通过分子技术进行确认，以避免假阳性结果，但它能够减少需要进行多重连接探针扩增分析的患者数量，对测试的周转时间产生积极影响。最后，由于分析的时间和成本与仅用于 BRCA1 基因的分析相似，因此这种策略可能负担得起提供更全面的遗传性癌症风险评估测试。
