维普中文期刊产品整合服务

Inflammation-associated microsatellite alterations:Mechanisms and significance in the prognosis of patients with colorectal cancer

查看全文 作　　者：Minoru [1]Koi;Stephanie S Tseng-[1]Rogenski;John M [1]Carethers 高影响力作者 机构地区：[1]Department of Internal Medicine and Comprehensive Cancer Center,University of Michigan,Ann Arbor,MI 48109-5368,United States高影响力机构 出　　处：《World Journal of Gastrointestinal Oncology》索引2018年第10卷第1期,共14页高影响力期刊 基　　金：Supported by United States Public Health Service,Nos.DK067287,CA162147 and CA206010;the A.Alfred Taubman Medical Research Institute of the University of Michigan 摘　　要：Microsatellite alterations within genomic DNA frameshift as a result of defective DNA mismatch repair(MMR). About 15% of sporadic colorectal cancers(CRCs) manifest hypermethylation of the DNA MMR gene MLH1, resulting in mono-and di-nucleotide frameshifts to classify it as microsatellite instability-high(MSI-H) and hypermutated, and due to frameshifts at coding microsatellites generating neo-antigens, produce a robust protective immune response that can be enhanced with immune checkpoint blockade. More commonly, approximately 50% of sporadic nonMSI-H CRCs demonstrate frameshifts at di-and tetra-nucleotide microsatellites to classify it as MSIlow/elevated microsatellite alterations at selected tetranucleotide repeats(EMAST) as a result of functional somatic inactivation of the DNA MMR protein MSH3 via a nuclear-to-cytosolic displacement. The trigger for MSH3 displacement appears to be inflammation and/or oxidative stress, and unlike MSI-H CRC patients, patients with MSI-L/EMAST CRCs show poor prognosis. These inflammatory-associated microsatellite alterations are a consequence of the local tumor microenvironment, and in theory, if the microenvironment is manipulated to lower inflammation, the microsatellite alterations and MSH3 dysfunction should be corrected. Here we describe the mechanisms and significance of inflammatory-associated microsatellite alterations, and propose three areas to deeply explore the consequences and prevention of inflammation's effect upon the DNA MMR system. 关 键 词：MICROSATELLITE instability MICROSATELLITE stable ELEVATED MICROSATELLITE alterations at selected TETRANUCLEOTIDE REPEATS Colorectal cancer MISMATCH repair INFLAMMATION MSH3
相关文献

参考文献(126)

引证文献(7)

耦合文献(1)

网站首页 | 关于我们 | 联系我们 | 产品服务 | 客服中心 | 广告服务 | 版权声明 | 网站联盟 | 友情链接 | 售卡网点

版权所有© 渝B2-20050021-1　渝公网安备 50019002500403号　违法和不良信息举报中心

互联网出版许可证 新出网证(渝)字10号 全国400电话 - 免长途话费