변이표현형 암에서 DNA 부정합 보수체계 유전자 산물의 발현
Expression Pattern of DNA Mismatch Repair Genes in Tumors of Microsatellite Mutator Phenotype
김정진, 백명진, 김남균, 김윤희, 김지은, 김호근, 박찬일,
소속 상세정보
김정진 ( Kim Jung-Jin )
연세대학교 의과대학 병리학교실
백명진 ( Baek Myung-Jin )
연세대학교 의과대학 병리학교실
김남균 ( Kim Nam-Gyun )
연세대학교 의과대학 병리학교실
김윤희 ( Kim Yun-Hee )
연세대학교 의과대학 병리학교실
김지은 ( Kim Ji-Eun )
연세대학교 의과대학 병리학교실
김호근 ( Kim Ho-Guen )
연세대학교 의과대학 병리학교실
박찬일 ( Park Chan-Il )
연세대학교 의과대학 병리학교실
KMID : 0357920000340090609
Abstract
Microsatellite mutator phenotype (MMP) tumors were reported in a subset of gastrointestinal carcinomas. The molecular pathogenesis of MMP tumors shows defects in the DNA mismatch repair genes, and also many germline and somatic mutations were reported in the MMP tumors. However, the detection of genetic defects in the MMP tumors is very difficult, mainly because many genes are included in the DNA mismatch repair genes. This study was undertaken to determine the best strategy for detecting defects in the DNA mismatch repair genes in gastrointestinal carcinomas. One of the effective ways for detecting defects in DNA mismatch repair genes is to screen the MMP tumors and evaluate the products of DNA mismatch repair genes by performing the multiplex RT-PCR method. We have screened the MMP tumors by using 5 microsatellite markers in the 12 cancer cell lines, 120 colon carcinomas and 99 gastric carcinomas and found 6 MMP cell lines, 10 MMP colon cancers, and 9 MMP gastric carcinomas. In addition, we evaluated 6 DNA mismatch repair gene products (hMSH2, hMSH3, hMSH6, hMLH1, hPMS1 and hPMS2) by multiplex RT-PCR analysis and found decreased expression of the DNA mismatch repair genes in 5 (hMSH6 in DLD-1 and HCT-15; hMSH2 in LoVo; hMLH1 and hMSH3 in HCT-116; hMLH1 in SNU-638) out of 6 MMP cell lines. We also found a decreased expression of hMLH1 in 3 out of 10 MMP colon carcinomas, and in 6 out of 9 MMP gastric carcinomas. Our results indicate that the expression analysis of the DNA mismatch repair genes by multiplex RT-PCR method can reduce the number of genes subjected to mutational analysis and is convenient for screening the responsible DNA mismatch repair genes.
키워드
Microsatellite mutator phenotype;DNA mismatch repair genes;Multiplex RT-PCR
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