Zhang Lihong, Peng Yang, Peng Guang
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, China.
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center Houston, Texas, USA.
Am J Cancer Res. 2018 Oct 1;8(10):1977-1988. eCollection 2018.
Mismatch repair (MMR) plays a key role in maintaining genomic stability. Mismatch repair deficiency (MMR-D) causes a molecular feature of microsatellite instability (MSI) and contributes to the development of human cancers and genetic diseases with cancer predisposition such as Lynch syndrome. Recent studies have shown that immune checkpoint blockade therapy has a promising response in MMR-D cancers regardless of the tissue of origin. Being able to identify patients with MMR-D cancers is an important challenge in clinical practice. Although immunohistochemistry (IHC) and polymerase chain reaction (PCR)-based MSI analysis combined with a subsequent MMR gene test are used as the standard of care in the clinical setting to identify patients with MMR-D cancers, these methods have limitations as a pan-cancer testing strategy. Next-generation sequencing (NGS) has developed and matured as a clinical option and NGS has advantages for use as a novel testing strategy for MMR-D detection. In this review, we describe the genetic basis of MMR-D, current diagnostic algorithms in the clinical management of MMR-D, the novel NGS approach, and potential detection strategy of anti-cancer immunity biomarkers of MMR-D.
错配修复（MMR）在维持基因组稳定性方面发挥着关键作用。错配修复缺陷（MMR-D）会导致微卫星不稳定性（MSI）这一分子特征，并促使人类癌症以及具有癌症易感性的遗传性疾病（如林奇综合征）的发生发展。最近的研究表明，无论肿瘤起源于何种组织，免疫检查点阻断疗法对MMR-D癌症都有显著疗效。能够识别MMR-D癌症患者是临床实践中的一项重要挑战。虽然免疫组织化学（IHC）和基于聚合酶链反应（PCR）的MSI分析并随后进行MMR基因检测在临床环境中被用作识别MMR-D癌症患者的标准治疗方法，但这些方法作为一种泛癌检测策略存在局限性。新一代测序（NGS）已发展成熟并成为一种临床选择，并且NGS作为一种用于检测MMR-D的新型检测策略具有优势。在本综述中，我们描述了MMR-D的遗传基础、MMR-D临床管理中的当前诊断算法、新型NGS方法以及MMR-D抗癌免疫生物标志物的潜在检测策略。
