Frequent Bax frameshift mutations in gastric cancer with high but not low microsatellite instability.
Widespread microsatellite instability (MSI) due to the defective DNA mismatch repair underlies the pathogenesis of the majority of hereditary non-polyposis colorectal cancer and a subset of various sporadic malignant tumors. Using 5 microsatellite markers and the criteria of MSI proposed by the National Cancer Institute (NCI) workshop, we analyzed 205 gastric adenocarcinomas for MSI. Based on the number of markers showing instability per tumor, the tumors were divided into three groups; those with two or more of the five markers displaying instability (high MSI, MSI-H), those with one of five markers displaying instability (low MSI, MSI-L), and those with no instability (microsatellite stable, MSS). Among 205 tumors, 30 (15%) were MSI-H, 15 (7%) were MSI-L, and 160 (78%) were MSS. All of the 30 MSI-H tumors demonstrated instability at BAT26, a sensitive marker for the widespread MSI, while none of the 15 MSI-L tumors did. MSI-H tumors were significantly associated with distal location and well or moderate differentiation, but MSI-L tumors were indistinguishable from MSS tumors. Bax frameshift mutations were detected in 60% of the 30 MSI-H tumors, while not in any of the 15 MSI-L tumors. These results suggest that microsatellite analysis using the criteria proposed by the NCI workshop may be appropriate for gastric cancers because it unveils real differences in genotype and phenotype.
Yamamoto
H
H
First Dept. of Internal Medicine, Sapporo Medical University, Japan.
Itoh
F
F
Fukushima
H
H
Adachi
Y
Y
Itoh
H
H
Hinoda
Y
Y
Imai
K
K
D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics* / Q000473:pathology*; D020137:Base Pair Mismatch; D004260:DNA Repair; D005260:Female; D016368:Frameshift Mutation; D019254:Genes, bcl-2; D005819:Genetic Markers; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D013274:Stomach Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D005819:Genetic Markers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein