title: Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype.
abstract: 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.
authors.affiliation: The Burnham Institute, La Jolla Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: N
authors.initials: N
authors.lastname: Rampino
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Ionov
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Sawai
authors.forename: J C
authors.initials: JC
authors.lastname: Reed
authors.forename: M
authors.initials: M
authors.lastname: Perucho
mesh_terms: 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
chemical_list: C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein