title: The Emergence of Pan-Cancer CIMP and Its Elusive Interpretation.
abstract: Epigenetic dysregulation is recognized as a hallmark of cancer. In the last 16 years, a CpG island methylator phenotype (CIMP) has been documented in tumors originating from different tissues. However, a looming question in the field is whether or not CIMP is a pan-cancer phenomenon or a tissue-specific event. Here, we give a synopsis of the history of CIMP and describe the pattern of DNA methylation that defines the CIMP phenotype in different cancer types. We highlight new conceptual approaches of classifying tumors based on CIMP in a cancer type-agnostic way that reveal the presence of distinct CIMP tumors in a multitude of The Cancer Genome Atlas (TCGA) datasets, suggesting that this phenotype may transcend tissue-type specificity. Lastly, we show evidence supporting the clinical relevance of CIMP-positive tumors and suggest that a common CIMP etiology may define new mechanistic targets in cancer treatment.
authors.affiliation: National Human Genome Research Institute, Rockville, MD 20852, USA. millerbf2@mail.nih.gov.
authors.forename: Brendan F
authors.initials: BF
authors.lastname: Miller
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. sanchezf@cbio.mskcc.org.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Vega
authors.affiliation: National Human Genome Research Institute, Rockville, MD 20852, USA. elnitski@mail.nih.gov.
authors.forename: Laura
authors.initials: L
authors.lastname: Elnitski
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D066264:Datasets as Topic; D044127:Epigenesis, Genetic; D006801:Humans; D009369:Neoplasms / Q000145:classification* / Q000235:genetics; D009928:Organ Specificity; D010641:Phenotype
keywords: CpG island methylator phenotype; DNA methylation; pan-cancer