Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype |
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Authors: | N Rampino H Yamamoto Y Ionov Y Li H Sawai JC Reed M Perucho |
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Affiliation: | The Burnham Institute, La Jolla Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. |
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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. |
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