Rampino N, Yamamoto H, Ionov Y, Li Y, Sawai H, Reed J C, Perucho M
The Burnham Institute, La Jolla Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Science. 1997 Feb 14;275(5302):967-9. doi: 10.1126/science.275.5302.967.
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.
微卫星突变体表型（MMP）的癌症在简单重复序列处表现出过度的基因组不稳定性。在检测的超过50%（41例中的21例）的人类MMP+结肠腺癌中，发现促凋亡基因BAX内一段八个脱氧鸟苷[(G)8]的序列存在移码突变。这些突变在MMP-肿瘤中不存在，并且在其他基因的(G)8重复序列中频率显著更低。在一些MMP+结肠肿瘤细胞系和原发性肿瘤的两个BAX等位基因中均存在移码突变。这些结果表明，在结直肠癌MMP+肿瘤进展过程中，BAX失活突变被选择，并且野生型BAX基因在结直肠癌发生的p53非依赖途径中起抑制作用。
