CpG island methylator phenotype in colorectal cancer
AUTOR(ES)
Toyota, Minoru
FONTE
The National Academy of Sciences
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17576Documentos Relacionados
- Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype
- Molecular correlates with MGMT promoter methylation and silencing support CpG island methylator phenotype‐low (CIMP‐low) in colorectal cancer
- A CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines
- Predicting aberrant CpG island methylation
- CpG island mapping of a mouse double-minute chromosome.