유전자 불안정성의 기전과 임상적 적용
Mechanism of Genomic Instability and Its Clinical Applications
이석환,
소속 상세정보
이석환 ( Lee Seok-Hwan )
경희대학교 의과대학 외과학교실
KMID : 0356720040200010064
Abstract
Multiple genetic alterations are common prerequisite for carcinogenesis including colorectal cancers (CRCs). Recently, mutations within microsatellites have been described as a result of defective DNA mismatch repair (MMR) mechanisms, resulting in the phenomenon of microsatellite instability (MSI). This has been implicated in the etiology of hereditary non-polyposis colorectal cancer (HNPCC) and significant portions of sporadic colorectal cancers. However, the mechanisms underlying the MSI are different from hereditary CRCs and sporadic CRCs. While the germline mutation of MMR genes is responsible for HNPCC, the hypermethylation of MLH1 gene promoter regions, an epigenetic, not inherited alteration is responsible for most sporadic CRCs showing MSI. MSI tumors exhibit characteristic clinco- pathologic features, i.e, tumors are preferentially located to proximal to splenic flexure, poorly differentiated, mucinous cell type, frequently showing peritumoral lymphocytic infiltration, and, of importance, showing better survival in stage- matched cases. In this article, the results of recent investigations about MSI and its clinical applications are comprehensively reviewed. Knowledge of these biochemical mechanisms are likely to lead to more effective diagnosis and therapy of CRCs in the future. J Korean Soc Coloproctol 2004;20:64-73
키워드
유전자 불안정성;현미부수체 불안정성;가족성 비용종증대장암;에피제네틱 변화
Genomic instability;Microsatellite instability;Hereditary non-polyposis colorectal cancer;Epigenetic alteration
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