Infrequent hMSH2 mutations in sporadic gastric adenocarcinoma with microsatellite instability.
The status of genetic instability was determined with seven microsatellite markers from 40 patients with primary gastric adenocarcinoma. For those cases with microsatellite instability, alterations of hMSH2 were further investigated by direct sequencing of reverse transcription-polymerase chain reaction products. Twelve (30%) of 40 patients were found to have microsatellite instability. Among them, one patient (1/6, 16.7%) was early gastric cancer and 11 (11/34, 32.4%) were advanced gastric cancer. There were seven patients with diffuse type (7/18, 38.7%), while five (5/22, 22.7%) were intestinal type tumors. The entire coding region of the hMSH2 gene in these 12 affected individuals was amplified and sequenced. Only a 41-year-old female patient with diffuse type advanced gastric cancer showed a GCT to TCT missense mutation at codon 207 with predicted protein change from alanine to serine. Our results indicate that genetic instability plays an important role in gastric tumorigenesis and alterations of the hMSH2 gene are related to only a small portion of sporadic gastric adenocarcinoma with microsatellite instability.
Wu
M S
MS
Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, ROC.
Sheu
J C
JC
Shun
C T
CT
Lee
W J
WJ
Wang
J T
JT
Wang
T H
TH
Cheng
A L
AL
Lin
J T
JT
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000235:genetics*; D004276:DNA, Satellite / Q000235:genetics*; D004268:DNA-Binding Proteins; D004586:Electrophoresis; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein; D009154:Mutation; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D004273:DNA, Neoplasm; D004276:DNA, Satellite; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein