Cortesi Laura, Piombino Claudia, Toss Angela
Genetic Oncology Unit, Department of Oncology and Haematology, University Hospital of Modena, 41125 Modena, Italy.
J Pers Med. 2021 Mar 28;11(4):245. doi: 10.3390/jpm11040245.
The homologous recombination repair (HRR) pathway repairs double-strand DNA breaks, mostly by BRCA1 and BRCA2, although other proteins such as ATM, CHEK2, and PALB2 are also involved. germline mutations are targeted by PARP inhibitors. The aim of this commentary is to explore whether germline mutations in HRR-related genes other than have to be considered as prognostic factors or predictive to therapies by discussing the results of two articles published in December 2020. The TBCRC 048 trial published by Tung et al. showed an impressive objective response rate to olaparib in metastatic breast cancer patients with germline mutation compared to germline and mutation carriers. Additionally, Yadav et al. observed a significantly longer overall survival in pancreatic adenocarcinoma patients with germline HRR mutations compared to non-carriers. In our opinion, assuming that is a high-penetrant gene with a key role in the HRR system, mutations are predictive factors for response to treatment. Moreover, germline mutations in the gene provide a better outcome in pancreatic adenocarcinoma, being more often associated to wild-type . In conclusion, sequencing of HRR-related genes other than should be routinely offered as part of a biological characterization of pancreatic and breast cancers.
同源重组修复（HRR）途径主要通过BRCA1和BRCA2修复双链DNA断裂，不过其他蛋白质如ATM、CHEK2和PALB2也参与其中。胚系突变可被PARP抑制剂靶向作用。本评论的目的是通过讨论2020年12月发表的两篇文章的结果，探讨除 外的HRR相关基因中的胚系突变是否必须被视为预后因素或治疗预测指标。Tung等人发表的TBCRC 048试验表明，与胚系 和 突变携带者相比，携带胚系 突变的转移性乳腺癌患者对奥拉帕尼有令人印象深刻的客观缓解率。此外，Yadav等人观察到，与非携带者相比，携带胚系HRR突变的胰腺腺癌患者的总生存期显著更长。在我们看来，假设 是一个在HRR系统中起关键作用的高 penetrant基因， 突变是治疗反应的预测因素。此外， 基因中的胚系突变在胰腺腺癌中预后更好，更常与野生型 相关。总之，除 外的HRR相关基因测序应作为胰腺癌和乳腺癌生物学特征描述的一部分常规进行。 （注：原文中“high-penetrant”和最后一处“ ”表述不完整，可能影响准确理解，但按要求忠实翻译）
