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CpG island methylator phenotypes in aging and cancer.
Semin Cancer Biol. 1999 Oct; 9(5):349-57.SC

Abstract

CpG islands are short stretches of CpG rich regions that are frequently associated with the promoter region of genes. Aberrant methylation of CpG islands is one mechanism of inactivating tumor suppressor genes (TSGs) in neoplasia, and there is growing evidence that altered cytosine methylation play important roles in cancer development. However, the differences in global CpG island methylation patterns between normal and cancer cells remain poorly understood. By examining a large number of loci in a series of cancers, global methylation profiles can be constructed. Such studies revealed that in colorectal cancer, there appears to be two types of methylation that are associated with cancer progression: type A (for age-related) methylation, and type C (for cancer-specific) methylation. Initially, type A methylation arises as a function of age in normal colorectal epithelial cells. By affecting genes that regulate the growth and/or differentiation of these cells, such methylation may result in a predisposition state that precedes tumor formation in the colon. Type C methylation, by contrast, was found exclusively in a subset of cancers, which display a CpG island methylator phenotype (CIMP). CIMP is a novel molecular instability pathway that appears to be responsible for most cases of aberrant TSG methylation in colorectal cancer, and which has important interactions with genetic pathways as well. In fact, CIMP+ tumors account for the majority of sporadic colorectal cancers with microsatellite instability, through methylation of the mismatch repair gene hMLH1. This model whereby age-related methylation increases cell-susceptibility to transformation and cancer-specific methylation results in neoplastic progression in a subset of cases may be applicable to many human neoplasms.

Authors+Show Affiliations

Johns Hopkins Oncology Center, 424 N. Bond Street, Baltimore, MD 21231, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

10547343

Citation

Toyota, M, and J P. Issa. "CpG Island Methylator Phenotypes in Aging and Cancer." Seminars in Cancer Biology, vol. 9, no. 5, 1999, pp. 349-57.
Toyota M, Issa JP. CpG island methylator phenotypes in aging and cancer. Semin Cancer Biol. 1999;9(5):349-57.
Toyota, M., & Issa, J. P. (1999). CpG island methylator phenotypes in aging and cancer. Seminars in Cancer Biology, 9(5), 349-57.
Toyota M, Issa JP. CpG Island Methylator Phenotypes in Aging and Cancer. Semin Cancer Biol. 1999;9(5):349-57. PubMed PMID: 10547343.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CpG island methylator phenotypes in aging and cancer. AU - Toyota,M, AU - Issa,J P, PY - 1999/11/5/pubmed PY - 1999/11/5/medline PY - 1999/11/5/entrez SP - 349 EP - 57 JF - Seminars in cancer biology JO - Semin Cancer Biol VL - 9 IS - 5 N2 - CpG islands are short stretches of CpG rich regions that are frequently associated with the promoter region of genes. Aberrant methylation of CpG islands is one mechanism of inactivating tumor suppressor genes (TSGs) in neoplasia, and there is growing evidence that altered cytosine methylation play important roles in cancer development. However, the differences in global CpG island methylation patterns between normal and cancer cells remain poorly understood. By examining a large number of loci in a series of cancers, global methylation profiles can be constructed. Such studies revealed that in colorectal cancer, there appears to be two types of methylation that are associated with cancer progression: type A (for age-related) methylation, and type C (for cancer-specific) methylation. Initially, type A methylation arises as a function of age in normal colorectal epithelial cells. By affecting genes that regulate the growth and/or differentiation of these cells, such methylation may result in a predisposition state that precedes tumor formation in the colon. Type C methylation, by contrast, was found exclusively in a subset of cancers, which display a CpG island methylator phenotype (CIMP). CIMP is a novel molecular instability pathway that appears to be responsible for most cases of aberrant TSG methylation in colorectal cancer, and which has important interactions with genetic pathways as well. In fact, CIMP+ tumors account for the majority of sporadic colorectal cancers with microsatellite instability, through methylation of the mismatch repair gene hMLH1. This model whereby age-related methylation increases cell-susceptibility to transformation and cancer-specific methylation results in neoplastic progression in a subset of cases may be applicable to many human neoplasms. SN - 1044-579X UR - https://www.unboundmedicine.com/medline/citation/10547343/CpG_island_methylator_phenotypes_in_aging_and_cancer_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1044-579X(99)90135-9 DB - PRIME DP - Unbound Medicine ER -