Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype.
Cancers of the microsatellite mutator phenotype (MMP) show exaggerated genomic instability at simple repeat sequences. More than 50 percent (21 out of 41) of human MMP+ colon adenocarcinomas examined were found to have frameshift mutations in a tract of eight deoxyguanosines [(G)8] within BAX, a gene that promotes apoptosis. These mutations were absent in MMP- tumors and were significantly less frequent in (G)8 repeats from other genes. Frameshift mutations were present in both BAX alleles in some MMP+ colon tumor cell lines and in primary tumors. These results suggest that inactivating BAX mutations are selected for during the progression of colorectal MMP+ tumors and that the wild-type BAX gene plays a suppressor role in a p53-independent pathway for colorectal carcinogenesis.
Rampino
N
N
The Burnham Institute, La Jolla Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Yamamoto
H
H
Ionov
Y
Y
Li
Y
Y
Sawai
H
H
Reed
J C
JC
Perucho
M
M
D000230:Adenocarcinoma / Q000235:genetics*; D000483:Alleles; D017209:Apoptosis; D001483:Base Sequence; D003110:Colonic Neoplasms / Q000235:genetics*; D016368:Frameshift Mutation; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein