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POLE/POLD1 mutation in non-exonuclease domain matters for predicting efficacy of immune-checkpoint-inhibitor therapy.

作者信息

Chen Yan-Xing, Wang Zi-Xian, Yuan Shu-Qiang, Jiang Teng-Jia, Huang You-Sheng, Xu Rui-Hua, Wang Feng, Zhao Qi

机构信息

State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, China.

Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, China.

出版信息

Clin Transl Med. 2021 Sep;11(9):e524. doi: 10.1002/ctm2.524.

DOI:10.1002/ctm2.524
PMID:34586735
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8473642/
Abstract
摘要

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POLE/POLD1 mutation in non-exonuclease domain matters for predicting efficacy of immune-checkpoint-inhibitor therapy.非外切酶结构域中的POLE/POLD1突变对预测免疫检查点抑制剂疗法的疗效至关重要。
Clin Transl Med. 2021 Sep;11(9):e524. doi: 10.1002/ctm2.524.
2
Proofreading the way: immune checkpoint inhibitors in polymerase ε/polymerase δ (POLE/POLD1)-altered colorectal cancer.校对方式：免疫检查点抑制剂在聚合酶ε/聚合酶δ（POLE/POLD1）改变的结直肠癌中的应用
Ann Oncol. 2024 Jul;35(7):582-584. doi: 10.1016/j.annonc.2024.04.006.
3
POLE/POLD1 mutation and tumor immunotherapy.POLE/POLD1 突变与肿瘤免疫治疗。
J Exp Clin Cancer Res. 2022 Jul 2;41(1):216. doi: 10.1186/s13046-022-02422-1.
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POLE and POLD1 germline exonuclease domain pathogenic variants, a rare event in colorectal cancer from the Middle East.POLE 和 POLD1 种系外切酶结构域致病性变异，在中东地区结直肠癌中罕见事件。
Mol Genet Genomic Med. 2020 Aug;8(8):e1368. doi: 10.1002/mgg3.1368. Epub 2020 Jun 22.
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POLE and POLD1 screening in 155 patients with multiple polyps and early-onset colorectal cancer.对155例多发息肉和早发性结直肠癌患者进行POLE和POLD1筛查。
Oncotarget. 2017 Apr 18;8(16):26732-26743. doi: 10.18632/oncotarget.15810.
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Low frequency of POLD1 and POLE exonuclease domain variants in patients with multiple colorectal polyps.多发性结直肠息肉患者中POLD1和POLE核酸外切酶结构域变异的低频率。
Mol Genet Genomic Med. 2019 Apr;7(4):e00603. doi: 10.1002/mgg3.603. Epub 2019 Mar 2.
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Functional landscapes of POLE and POLD1 mutations in checkpoint blockade-dependent antitumor immunity.POLE 和 POLD1 突变在依赖于检查点阻断的抗肿瘤免疫中的功能景观。
Nat Genet. 2022 Jul;54(7):996-1012. doi: 10.1038/s41588-022-01108-w. Epub 2022 Jul 11.
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High mutational burden in colorectal carcinomas with monoallelic POLE mutations: absence of allelic loss and gene promoter methylation.POLE 单等位基因突变的结直肠癌中存在高突变负担：不存在等位基因缺失和基因启动子甲基化。
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Risk of colorectal cancer for carriers of a germ-line mutation in POLE or POLD1.胚系 POLE 或 POLD1 基因突变携带者结直肠癌风险。
Genet Med. 2018 Aug;20(8):890-895. doi: 10.1038/gim.2017.185. Epub 2017 Nov 9.
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POLD1 and POLE Gene Mutations in Jewish Cohorts of Early-Onset Colorectal Cancer and of Multiple Colorectal Adenomas.POLD1 和 POLE 基因突变在早发性结直肠癌和多发性结直肠腺瘤的犹太人群体中的研究。
Dis Colon Rectum. 2018 Sep;61(9):1073-1079. doi: 10.1097/DCR.0000000000001150.

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Beyond proofreading: POLD1 mutations as dynamic orchestrators of genomic instability and immune evasion in cancer.超越校对：POLD1突变作为癌症基因组不稳定和免疫逃逸的动态调控因子
Front Immunol. 2025 Jun 30;16:1600233. doi: 10.3389/fimmu.2025.1600233. eCollection 2025.
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POLE mutations in endometrial carcinoma: Clinical and genomic landscape from a large prospective single-center cohort.子宫内膜癌中的POLE突变：来自大型前瞻性单中心队列的临床和基因组概况
Cancer. 2025 Feb 1;131(3):e35731. doi: 10.1002/cncr.35731.
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PD-L1 as a Biomarker in Gastric Cancer Immunotherapy.

本文引用的文献

1
Advancing to the era of cancer immunotherapy.迈入癌症免疫治疗时代。
Cancer Commun (Lond). 2021 Sep;41(9):803-829. doi: 10.1002/cac2.12178. Epub 2021 Jun 24.
2
The repertoire of mutational signatures in human cancer.人类癌症中的突变特征谱。
Nature. 2020 Feb;578(7793):94-101. doi: 10.1038/s41586-020-1943-3. Epub 2020 Feb 5.
3
Evaluation of POLE and POLD1 Mutations as Biomarkers for Immunotherapy Outcomes Across Multiple Cancer Types.评估POLE和POLD1突变作为多种癌症类型免疫治疗结果生物标志物的研究
程序性死亡受体配体1作为胃癌免疫治疗中的生物标志物
J Gastric Cancer. 2025 Jan;25(1):177-191. doi: 10.5230/jgc.2025.25.e4.
4
The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update.中国临床肿瘤学会（CSCO）：《中国结直肠癌诊疗规范（2024年版）》
Cancer Commun (Lond). 2025 Mar;45(3):332-379. doi: 10.1002/cac2.12639. Epub 2024 Dec 31.
5
A phase II clinical trial of toripalimab in advanced solid tumors with polymerase epsilon/polymerase delta (POLE/POLD1) mutation.在具有聚合酶 epsilon/聚合酶 delta（POLE/POLD1）突变的晚期实体瘤中进行的特泊替尼的 II 期临床试验。
Signal Transduct Target Ther. 2024 Sep 2;9(1):227. doi: 10.1038/s41392-024-01939-5.
6
Combined anti-PD-1, HDAC inhibitor and anti-VEGF for MSS/pMMR colorectal cancer: a randomized phase 2 trial.抗 PD-1、HDAC 抑制剂和抗 VEGF 联合治疗 MSS/pMMR 结直肠癌：一项随机 2 期试验。
Nat Med. 2024 Apr;30(4):1035-1043. doi: 10.1038/s41591-024-02813-1. Epub 2024 Mar 4.
7
Race, Prevalence of POLE and POLD1 Alterations, and Survival Among Patients With Endometrial Cancer.种族、POLE 和 POLD1 改变的流行率以及子宫内膜癌患者的生存。
JAMA Netw Open. 2024 Jan 2;7(1):e2351906. doi: 10.1001/jamanetworkopen.2023.51906.
8
Rare germline variants in POLE and POLD1 encoding the catalytic subunits of DNA polymerases ε and δ in glioma families.在胶质瘤家系中，编码 DNA 聚合酶 ε 和 δ 催化亚基的 POLE 和 POLD1 中罕见的种系变异。
Acta Neuropathol Commun. 2023 Nov 21;11(1):184. doi: 10.1186/s40478-023-01689-5.
9
The current status and prospect of immunotherapy in colorectal cancer.结直肠癌免疫治疗的现状与展望。
Clin Transl Oncol. 2024 Jan;26(1):39-51. doi: 10.1007/s12094-023-03235-0. Epub 2023 Jun 10.
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Current Progress on Predictive Biomarkers for Response to Immune Checkpoint Inhibitors in Gastric Cancer: How to Maximize the Immunotherapeutic Benefit?胃癌中免疫检查点抑制剂反应预测生物标志物的当前进展：如何最大化免疫治疗益处？
Cancers (Basel). 2023 Apr 13;15(8):2273. doi: 10.3390/cancers15082273.
JAMA Oncol. 2019 Oct 1;5(10):1504-1506. doi: 10.1001/jamaoncol.2019.2963.
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Tumor mutational load predicts survival after immunotherapy across multiple cancer types.肿瘤突变负荷可预测多种癌症类型免疫治疗后的生存情况。
Nat Genet. 2019 Feb;51(2):202-206. doi: 10.1038/s41588-018-0312-8. Epub 2019 Jan 14.
5
Comprehensive Analysis of Hypermutation in Human Cancer.人类癌症中高突变的综合分析。
Cell. 2017 Nov 16;171(5):1042-1056.e10. doi: 10.1016/j.cell.2017.09.048. Epub 2017 Oct 19.
6
Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas.胚系突变影响 POLE 和 POLD1 的校对结构域，易导致结直肠腺瘤和癌。
Nat Genet. 2013 Feb;45(2):136-44. doi: 10.1038/ng.2503. Epub 2012 Dec 23.