Germline Mutations in Other Homologous Recombination Repair-Related Genes Than BRCA1/2: Predictive or Prognostic Factors?
Germline Mutations in Other Homologous Recombination Repair-Related Genes Than BRCA1/2: Predictive or Prognostic Factors?
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DOI：
10.3390/jpm11040245
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发表时间：
2021-03-28
影响因子：
--
通讯作者：
Toss A
中科院分区：
文献类型：
--
作者：
Cortesi L;Piombino C;Toss A
同源重组修复（HRR）途径修复双链DNA断裂，主要通过BRCA1和BRCA2，尽管其他蛋白如ATM、CHEK2和PALB2也参与其中。BRCA1/2种系突变是PARP抑制剂的靶标。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BRCA1/2以外的hrr相关基因的种系突变是否必须被视为预后因素或预测治疗的因素。Tung等人发表的TBCRC 048试验显示，与种系ATM和CHEK2突变携带者相比，携带PALB2突变的转移性乳腺癌患者对奥拉帕尼的客观反应率令人印象深刻。此外，Yadav等人观察到，与非携带者相比，生殖系HRR突变的胰腺腺癌患者的总生存期明显更长。我们认为，假设PALB2是一个高渗透基因，在HRR系统中起关键作用，PALB2突变是对治疗反应的预测因素。此外，ATM基因的种系突变在胰腺腺癌中提供了更好的结果，更常与野生型KRAS相关。总之，除BRCA1/2外，hrr相关基因的测序应作为胰腺癌和乳腺癌生物学特征的一部分常规提供。
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. BRCA1/2 germline mutations are targeted by PARP inhibitors. The aim of this commentary is to explore whether germline mutations in HRR-related genes other than BRCA1/2 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 PALB2 mutation compared to germline ATM and CHEK2 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 PALB2 is a high-penetrant gene with a key role in the HRR system, PALB2 mutations are predictive factors for response to treatment. Moreover, germline mutations in the ATM gene provide a better outcome in pancreatic adenocarcinoma, being more often associated to wild-type KRAS. In conclusion, sequencing of HRR-related genes other than BRCA1/2 should be routinely offered as part of a biological characterization of pancreatic and breast cancers.
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DOI：
10.1038/nrg3493
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
45.3
作者：
Cybulski, Cezary;Wokolorczyk, Dominika;Lubinski, Jan
通讯作者：
Lubinski, Jan
影响因子：
4
作者：
Jones, Tarsha;McCarthy, Anne Marie;Armstrong, Katrina
通讯作者：
Armstrong, Katrina
影响因子：
16
作者：
Ciccia A;Elledge SJ
通讯作者：
Elledge SJ
影响因子：
3.7
作者：
Kapoor, Nimmi S.;Curcio, Lisa D.;Banks, Kimberly C.
通讯作者：
Banks, Kimberly C.