Laboratory for Bioinformatics, Foundation Jean Dausset - CEPH, Paris, France.
Laboratory for Genomics, Foundation Jean Dausset - CEPH, Paris, France.
Adv Exp Med Biol. 2022;1361:75-100. doi: 10.1007/978-3-030-91836-1_5.
Microsatellite instability (MSI) is a genetic alteration due to a deficiency of the DNA mismatch repair system, where microsatellites accumulate insertions/deletions. This phenotype has been extensively characterized in colorectal cancer and is also sought in the context of Lynch syndrome diagnosis. It has recently been described in dozens of cancer types from whole genome/exome sequencing data, bearing some prognostic information. Moreover, MSI has also proven to be a major predicator of the response to immune checkpoint blockade therapy in solid cancer patients. Among the different methods developed for MSI detection in cancer, next-generation sequencing (NGS) is a promising and versatile technology offering many possibilities and advantages in diverse clinical applications compared to the gold standard PCR and capillary electrophoresis approach. NGS could notably increase the number of analyzed microsatellites and potentially be used to analyze other genetic alterations required for precision oncology. However, it requires the development of robust new computational algorithms for the analysis of NGS microsatellite data. In this chapter, we describe the different approaches developed for the assessment of MSI from NGS data in cancer, including the different microsatellite panels and computational algorithms proposed, highlighting their advantages and drawbacks, and their evaluation in different clinical applications.
微卫星不稳定性（MSI）是由于 DNA 错配修复系统缺陷导致的遗传改变，微卫星在此过程中积累插入/缺失。这种表型在结直肠癌中得到了广泛的描述，并且也在林奇综合征诊断的背景下进行了研究。最近，通过全基因组/外显子测序数据，在几十种癌症类型中也描述了这种表型，并且具有一定的预后信息。此外，MSI 也被证明是实体瘤患者对免疫检查点阻断治疗反应的主要预测因子。在用于癌症 MSI 检测的不同方法中，下一代测序（NGS）是一种很有前途和多功能的技术，与金标准 PCR 和毛细管电泳方法相比，在各种临床应用中提供了许多可能性和优势。NGS 可以显著增加分析的微卫星数量，并有可能用于分析其他需要精准肿瘤学的遗传改变。然而，它需要开发强大的新计算算法来分析 NGS 微卫星数据。在本章中，我们描述了从癌症 NGS 数据中评估 MSI 的不同方法，包括提出的不同微卫星面板和计算算法，强调了它们的优点和缺点，以及它们在不同临床应用中的评估。
