CpG island methylator phenotype in colorectal cancer

Minoru Toyota, Nita Ahuja, Mutsumi Ohe-Toyota, James G. Herman, Stephen B. Baylin, Jean Pierre J. Issa

Research output: Contribution to journalArticlepeer-review

Abstract

Aberrant methylation of promoter region CpG islands is associated with transcriptional inactivation of tumor, suppressor genes in neoplasia. To understand global patterns of CpG island methylation in colorectal cancer, we have used a recently developed technique called methylated CpG island amplification to examine 30 newly cloned differentially methylated DNA sequences. Of these 30 clones, 19 (63%) were progressively methylated in an age-dependent manner in normal colon, 7 (23%) were methylated in a cancer- specific manner, and 4 (13%) were methylated only in cell lines. Thus, a majority of CpG islands methylated in colon cancer are also methylated in a subset of normal colonic cells during the process of aging. In contrast, methylation of the cancer-specific clones was found exclusively in a subset of colorectal cancers, which appear to display a CpG island methylator phenotype (CIMP). CIMP+ tumors also have a high incidence of p16 and THBS1 methylation, and they include the majority of sporadic colorectal cancers with microsatellite instability related to hMLH1 methylation. We thus define a pathway in colorectal cancer that appears to be responsible for the majority of sporadic tumors with mismatch repair deficiency.

Original languageEnglish (US)
Pages (from-to)8681-8686
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number15
DOIs
StatePublished - Jul 20 1999

ASJC Scopus subject areas

  • General

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