{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361699995486714368.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1101/gr.117523.110"}},{"identifier":{"@type":"URI","@value":"https://syndication.highwire.org/content/doi/10.1101/gr.117523.110"}}],"dc:title":[{"@value":"Genome-scale analysis of aberrant DNA methylation in colorectal cancer"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Colorectal cancer (CRC) is a heterogeneous disease in which unique subtypes are characterized by distinct genetic and epigenetic alterations. Here we performed comprehensive genome-scale DNA methylation profiling of 125 colorectal tumors and 29 adjacent normal tissues. We identified four DNA methylation–based subgroups of CRC using model-based cluster analyses. Each subtype shows characteristic genetic and clinical features, indicating that they represent biologically distinct subgroups. A CIMP-high (CIMP-H) subgroup, which exhibits an exceptionally high frequency of cancer-specific DNA hypermethylation, is strongly associated with <jats:italic>MLH1</jats:italic> DNA hypermethylation and the <jats:italic>BRAF<jats:sup>V600E</jats:sup></jats:italic> mutation. A CIMP-low (CIMP-L) subgroup is enriched for <jats:italic>KRAS</jats:italic> mutations and characterized by DNA hypermethylation of a subset of CIMP-H-associated markers rather than a unique group of CpG islands. Non-CIMP tumors are separated into two distinct clusters. One non-CIMP subgroup is distinguished by a significantly higher frequency of <jats:italic>TP53</jats:italic> mutations and frequent occurrence in the distal colon, while the tumors that belong to the fourth group exhibit a low frequency of both cancer-specific DNA hypermethylation and gene mutations and are significantly enriched for rectal tumors. Furthermore, we identified 112 genes that were down-regulated more than twofold in CIMP-H tumors together with promoter DNA hypermethylation. These represent ∼7% of genes that acquired promoter DNA methylation in CIMP-H tumors. Intriguingly, 48/112 genes were also transcriptionally down-regulated in non-CIMP subgroups, but this was not attributable to promoter DNA hypermethylation. Together, we identified four distinct DNA methylation subgroups of CRC and provided novel insight regarding the role of CIMP-specific DNA hypermethylation in gene silencing.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381699995486714377","@type":"Researcher","foaf:name":[{"@value":"Toshinori Hinoue"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995486714371","@type":"Researcher","foaf:name":[{"@value":"Daniel J. Weisenberger"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995486714370","@type":"Researcher","foaf:name":[{"@value":"Christopher P.E. Lange"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995486714240","@type":"Researcher","foaf:name":[{"@value":"Hui Shen"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995486714375","@type":"Researcher","foaf:name":[{"@value":"Hyang-Min Byun"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995486714374","@type":"Researcher","foaf:name":[{"@value":"David Van Den Berg"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995486714373","@type":"Researcher","foaf:name":[{"@value":"Simeen Malik"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995486714369","@type":"Researcher","foaf:name":[{"@value":"Fei Pan"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995486714368","@type":"Researcher","foaf:name":[{"@value":"Houtan Noushmehr"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995486714376","@type":"Researcher","foaf:name":[{"@value":"Cornelis M. van Dijk"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995486714372","@type":"Researcher","foaf:name":[{"@value":"Rob A.E.M. Tollenaar"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995486714241","@type":"Researcher","foaf:name":[{"@value":"Peter W. Laird"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"10889051"},{"@type":"PISSN","@value":"http://id.crossref.org/issn/10889051"}],"prism:publicationName":[{"@value":"Genome Research"}],"dc:publisher":[{"@value":"Cold Spring Harbor Laboratory"}],"prism:publicationDate":"2011-06-09","prism:volume":"22","prism:number":"2","prism:startingPage":"271","prism:endingPage":"282"},"reviewed":"false","url":[{"@id":"https://syndication.highwire.org/content/doi/10.1101/gr.117523.110"}],"createdAt":"2011-06-10","modifiedAt":"2021-11-18","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360002214455035264","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Aberrant promoter methylation of <i>PPP1R3C</i> and <i>EFHD1</i> in plasma of colorectal cancer patients"}]},{"@id":"https://cir.nii.ac.jp/crid/1360002215789888768","@type":"Article","resourceType":"学術雑誌論文(journal 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metastatic behavior of colorectal cancer identified by array‐based comparative genomic hybridization"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004230481392000","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Quantitative DNA Methylation Analysis for Epigenotyping of Colorectal Cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004237551959552","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Distinct Molecular Features of Different Macroscopic Subtypes of Colorectal Neoplasms"}]},{"@id":"https://cir.nii.ac.jp/crid/1360021390753354240","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Enrichment of Bacteroides fragilis and enterotoxigenic Bacteroides fragilis in CpG island methylator phenotype-high colorectal 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