Metaxas Georgios I, Tsiambas Evangelos, Marinopoulos Spyridon, Adamopoulou Maria, Spyropoulou Despoina, Falidas Evangelos, Davris Dimitrios, Manaios Loukas, Fotiades Panagiotis, Mastronikoli Sofianiki, Peschos Dimitrios, Dimitrakakis Constantine
Breast Unit, 1st Department of Obstetrics and Gynaecology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Department of Cytology, 417 VA (NIMTS) Hospital, Athens, Greece.
Cancer Diagn Progn. 2023 Mar 3;3(2):169-174. doi: 10.21873/cdp.10197. eCollection 2023 Mar-Apr.
DNA mismatch repair system (MMR) is considered a leading genetic mechanism in stabilizing DNA structure and maintaining its function. DNA MMR is a highly conserved system in bacteria, prokaryotic, and eukaryotic cells, and provides the highest protection to DNA by repairing micro-structural alterations. DNA MMR proteins are involved in the detection and repair of intra-nucleotide base-to-base errors inside the complementary DNA strand recognizing the recently synthesized strand from the parental template. During DNA replication, a spectrum of errors including base insertion, deletion, and miss-incorporation negatively affect the molecule's structure and its functional stability. A broad spectrum of genomic alterations such as promoter hyper methylation, mutation, and loss of heterozygosity (LOH) in MMR genes including predominantly hMLH1, hMSH2, hMSH3, hMSH6, hPMS1, and hPMS2 lead to their loss of base-to-base error repairing procedure. Microsatellite instability (MSI) refers to the DNA MMR gene alterations that are observed in a variety of malignancies of different histological origins. In the current review, we present the role of DNA MMR deficiency in breast adenocarcinoma, a leading cancer-based cause of death in females worldwide.
DNA错配修复系统（MMR）被认为是稳定DNA结构和维持其功能的主要遗传机制。DNA错配修复是细菌、原核生物和真核细胞中高度保守的系统，通过修复微观结构改变为DNA提供最高级别的保护。DNA错配修复蛋白参与检测和修复互补DNA链内核苷酸之间的碱基错配，识别来自亲本模板的最近合成链。在DNA复制过程中，包括碱基插入、缺失和错掺入在内的一系列错误会对分子结构及其功能稳定性产生负面影响。多种基因组改变，如MMR基因（主要包括hMLH1、hMSH2、hMSH3、hMSH6、hPMS1和hPMS2）中的启动子高甲基化、突变和杂合性缺失（LOH），会导致其碱基错配修复过程丧失。微卫星不稳定性（MSI）指在不同组织学起源的多种恶性肿瘤中观察到的DNA错配修复基因改变。在本综述中，我们阐述了DNA错配修复缺陷在乳腺腺癌中的作用，乳腺腺癌是全球女性主要的癌症死亡原因。
