Microsatellite Instability Pathway and EMAST in Colorectal Cancer.
Microsatellite Instability Pathway and EMAST in Colorectal Cancer.
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DOI：
10.1007/s11888-017-0352-y
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发表时间：
2017-02
影响因子：
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通讯作者：
Carethers JM
中科院分区：
文献类型：
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作者：
Carethers JM
微卫星不稳定性（Microsatellite instability， MSI）是指对基因组DNA的移帧微卫星序列进行生化检测。MSI的发生是由于DNA错配修复（MMR）缺陷，无法纠正微卫星DNA复制后的滑移错误。估计有10万个基因组微卫星中的大多数是非编码的；然而，约150-300个微卫星正在编码，当在MSI肿瘤发病过程中移帧时，可以产生免疫原性新肽抗原，限制肿瘤的生长并延长患者的生存期。除了免疫反应和更长的生存期外，MSI结直肠癌患者往往有低分化的肿瘤，具有粘液特征，位于右结肠。MSI肿瘤患者对基于5-氟尿嘧啶的辅助化疗更耐药，但可能对PD-1免疫检查点阻断有反应。MMR功能的特定缺陷不仅会驱动MSI，还会提高选定的四核苷酸重复序列的微卫星改变，从而进一步改变患者的预后。
Microsatellite instability (MSI) refers to the biochemical detection of frameshifted microsatellite sequences from genomic DNA. Genesis of MSI is due to defective DNA mismatch repair (MMR) that fails to correct post DNA replicative slippage mistakes at microsatellites. Most of the estimated 100,000 genomic microsatellites are non-coding; however, ~150–300 microsatellites are coding such that, when frameshifted during the pathogenesis of an MSI tumor, can generate immunogenic neopeptide antigens that limit the growth of tumor and prolong patient survival. In addition to the immune reaction and longer survival, patients with MSI colorectal cancers tend to have poorly differentiated tumors with mucinous features that are located in the right colon. Patients with MSI tumors are more resistant to 5-fluorouracil-based adjuvant chemotherapy but may be responsive to PD-1 immune checkpoint blockade. Specific defects of MMR function not only drive MSI but also elevate microsatellite alterations at selected tetranucleotide repeats that may further modify patient outcome.