Laboratory for Personalized Medicine, Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka cesta 54, 10000 Zagreb, Croatia.
Genes (Basel). 2023 Jul 19;14(7):1474. doi: 10.3390/genes14071474.
Microsatellite instability (MSI) represents an accumulation of frameshifts in short tandem repeats, microsatellites, across the genome due to defective DNA mismatch repair (dMMR). MSI has been associated with distinct clinical, histological, and molecular features of tumors and has proven its prognostic and therapeutic value in different types of cancer. Recently, another type of microsatellite instability named elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) has been reported across many different tumors. EMAST tumors have been associated with chronic inflammation, higher tumor stage, and poor prognosis. Nevertheless, the clinical significance of EMAST and its relation to MSI remains unclear. It has been proposed that EMAST arises as a result of isolated MSH3 dysfunction or as a secondary event in MSI tumors. Even though previous studies have associated EMAST with MSI-low phenotype in tumors, recent studies show a certain degree of overlap between EMAST and MSI-high tumors. However, even in stable tumors, (MSS) frameshifts in microsatellites can be detected as a purely stochastic event, raising the question of whether EMAST truly represents a distinct type of microsatellite instability. Moreover, a significant fraction of patients with MSI tumors do not respond to immunotherapy and it can be speculated that in these tumors, EMAST might act as a modifying factor.
微卫星不稳定性 (MSI) 代表由于 DNA 错配修复 (dMMR) 缺陷而导致基因组中短串联重复序列（微卫星）的大量移码。MSI 与肿瘤的独特临床、组织学和分子特征相关，并已在不同类型的癌症中证明了其预后和治疗价值。最近，在许多不同的肿瘤中报告了另一种类型的微卫星不稳定性，称为选定四核苷酸重复序列的升高微卫星改变 (EMAST)。EMAST 肿瘤与慢性炎症、更高的肿瘤分期和不良预后相关。然而，EMAST 的临床意义及其与 MSI 的关系仍不清楚。有人提出 EMAST 是由于 MSH3 功能失调或 MSI 肿瘤中的继发事件引起的。尽管先前的研究将 EMAST 与肿瘤中的 MSI-低表型相关联，但最近的研究表明 EMAST 与 MSI-高肿瘤之间存在一定程度的重叠。然而，即使在稳定的肿瘤中，微卫星中的（MSS）移码也可以作为纯粹的随机事件检测到，这引发了一个问题，即 EMAST 是否真的代表了一种独特的微卫星不稳定性。此外，一部分 MSI 肿瘤患者对免疫治疗没有反应，人们可以推测，在这些肿瘤中，EMAST 可能充当修饰因子。
