Microsatellite instability with promoter methylation and silencing of hMLH1 can regionally occur during progression of gastric carcinoma.
Microsatellite instability (MSI) is known to result from inactivation of mismatch repair genes largely by promoter methylation. However, the methylation usually accumulates time-dependently. To know whether MSI can be acquired later in tumorigenesis, we examined intratumoral heterogeneity of MSI and promoter methylation of hMLH1 after immunohistochemical screening for heterogeneous expression of hMLH1 in 55 cases of gastric carcinomas. We demonstrated for the first time that MSI-H can develop from MSI-L or the absence of MSI due to time-dependent accumulation of DNA methylation during progression of early-stage gastric carcinomas. The resultant replication errors may play a role in enhancing invasive activity.
Ling
Zhi-Qiang
ZQ
Department of Pathology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan.
Tanaka
Aiko
A
Li
Pei
P
Nakayama
Takahisa
T
Fujiyama
Yoshihide
Y
Hattori
Takanori
T
Sugihara
Hiroyuki
H
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D004260:DNA Repair; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1