Microsatellite instability in colorectal cancer.
Microsatellite instability in colorectal cancer.
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DOI：
10.23750/abm.v89i9-s.7960
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发表时间：
2018-12-17
期刊：
影响因子：
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通讯作者：
Negri, Francesca
中科院分区：
文献类型：
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作者：
De' Angelis, Gian Luigi;Bottarelli, Lorena;Negri, Francesca
微卫星是分布在整个人类基因组中的 1 至 4 个碱基对的短串联重复 DNA 序列，包括编码区和非编码区。由于其重复的结构，微卫星特别容易出现复制错误，这些错误通常由错配修复（MMR）系统修复。 MMR 是一个非常高度保守的细胞过程，涉及许多蛋白质，导致错配碱基的识别和随后的修复，这些碱基可能在 DNA 复制、基因重组或化学或物理损伤过程中出现。 MMR 系统内的蛋白质包括 MLH1、PMS2、MSH2、MSH6、MLH3、MSH3、PMS1 和 Exo1。错配修复 (dMMR) 缺陷会导致被称为微卫星不稳定性 (MSI) 的强突变表型，其特征是由于 DNA 聚合酶滑移而导致微卫星序列出现广泛的长度多态性。 MSI被认为是结直肠癌（CRC）的主要致癌途径之一：它代表了遗传性非息肉病性结直肠癌（HNPCC），也称为林奇综合征（LS）的分子标志；此外，它在 15% 的散发性结直肠癌中被发现，更常见的是由于 MLH1 的表观遗传失活。 MSI CRC 的鉴定非常重要，因为 MSI 可作为检测 LS 的筛查工具、患者结果的预后标记以及对化疗和免疫治疗反应的预测标记。
Microsatellites are short tandem repeat DNA sequences of one to tetra base pairs distributed throughout the human genome, both in coding and non-coding regions. Owing to their repeated structure, microsatellites are particularly prone to replication errors that are normally repaired by the Mismatch Repair (MMR) system. MMR is a very highly conserved cellular process, involving many proteins, resulting in the identification, and subsequent repair of mismatched bases, likely to have arisen during DNA replication, genetic recombination or chemical or physical damage. Proteins within the MMR system include MLH1, PMS2, MSH2, MSH6, MLH3, MSH3, PMS1, and Exo1. Deficient MMR (dMMR) results in a strong mutator phenotype known as microsatellite instability (MSI), characterized by widespread length polymorphisms of microsatellite sequences due to DNA polymerase slippage. MSI is recognized as one of the major carcinogenetic pathways of colorectal cancer (CRC): it represents a molecular hallmark of hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome (LS); moreover it is detected in 15% of sporadic colorectal cancers, more often due to an epigenetic inactivation of MLH1. Identification of MSI CRC is important, as MSI may serve as a screening tool for detecting LS, a prognostic marker for patient outcome, and a predictive marker for response to chemotherapy and to immunotherapy.