Genetics supersedes epigenetics in colon cancer phenotype

被引:158
作者
Yamashita, K [1 ]
Dai, T [1 ]
Dai, Y [1 ]
Yamamoto, F [1 ]
Perucho, M [1 ]
机构
[1] La Jolla Canc Ctr, Burnham Inst, Canc Genet & Epigenet Program, La Jolla, CA 92037 USA
关键词
D O I
10.1016/S1535-6108(03)00190-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
A CpG island DNA methylator phenotype has been postulated to explain silencing of the hMLH1 DNA mismatch repair gene in cancer of the microsatellite mutator phenotype. To evaluate this model, we analyzed methylation in CpG islands from six mutator and suppressor genes, and thirty random genomic sites, in a panel of colorectal cancers. Tumor-specific somatic hypermethylation was a widespread age-dependent process that followed a normal Gaussian distribution. Because there was no discontinuity in methylation rate, our results challenge the methylator phenotype hypothesis and its hypothetical pathological underlying defect. We also show that the mutator phenotype dominates over the gradual accumulation of DNA hypermethylation in determining the genotypic features that govern the phenotypic peculiarities of colon cancer of the mutator pathway.
引用
收藏
页码:121 / 131
页数:11
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