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Cancer Res. 2013 Oct 1;73(19):5858-68. doi: 10.1158/0008-5472.CAN-12-4306. Epub 2013 Jun 25.

The CpG island methylator phenotype: what's in a name?

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Authors' Affiliations: Departments of Epidemiology and Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht; Department of Surgery, Orbis Medical Center, Sittard-Geleen; Department of Pathology, Leiden University Medical Center, Leiden; Department of Neurology, Erasmus University Medical Center, Erasmus University, Rotterdam, the Netherlands; Department of Mathematical Modeling, Statistics and Bioinformatics, Ghent University, Ghent, Belgium; and The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Abstract

Although the CpG island methylator phenotype (CIMP) was first identified and has been most extensively studied in colorectal cancer, the term "CIMP" has been repeatedly used over the past decade to describe CpG island promoter methylation in other tumor types, including bladder, breast, endometrial, gastric, glioblastoma (gliomas), hepatocellular, lung, ovarian, pancreatic, renal cell, and prostate cancers, as well as for leukemia, melanoma, duodenal adenocarninomas, adrenocortical carcinomas, and neuroblastomas. CIMP has been reported to be useful for predicting prognosis and response to treatment in a variety of tumor types, but it remains unclear whether or not CIMP is a universal phenomenon across human neoplasia or if there should be cancer-specific definitions of the phenotype. Recently, it was shown that somatic isocitrate dehydrogenase-1 (IDH1) mutations, frequently observed in gliomas, establish CIMP in primary human astrocytes by remodeling the methylome. Interestingly, somatic IDH1 and IDH2 mutations, and loss-of-function mutations in ten-eleven translocation (TET) methylcytosine dioxygenase-2 (TET2) associated with a hypermethylation phenotype, are also found in multiple enchondromas of patients with Ollier disease and Mafucci syndrome, and leukemia, respectively. These data provide the first clues for the elucidation of a molecular basis for CIMP. Although CIMP appears as a phenomenon that occurs in various cancer types, the definition is poorly defined and differs for each tumor. The current perspective discusses the use of the term CIMP in cancer, its significance in clinical practice, and future directions that may aid in identifying the true cause and definition of CIMP in different forms of human neoplasia.

PMID:
23801749
DOI:
10.1158/0008-5472.CAN-12-4306
[Indexed for MEDLINE]
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