title: Reconciliation of classification systems defining molecular subtypes of colorectal cancer: interrelationships and clinical implications.
abstract: Recently we published two independent studies describing novel gene expression-based classifications of colorectal cancer (CRC). Notably, each study stratified CRC into a different number of subtypes: one reported 3 subtypes, whereas the second highlighted 5. Given that each ascribed clinical significance, distinctive biology, and therapeutic prognosis to the different subtypes, we sought to reconcile this apparent incongruity in subtype stratification of CRC, and to interrelate the results. To do so, we each evaluated the other's data sets and analytical methods and discovered that the subtypes and their classifiers are, in fact, clearly related to each other; indeed, the 5 subtype outcomes can be coalesced into the same three. In addition to presenting this clarification, we briefly discuss how both classification methods can be viewed within the broader literature on CRC subtypes, and potentially applied.
authors.affiliation: Swiss Institute of Bioinformatics; Lausanne, Switzerland; Swiss Institute for Experimental Cancer Research; Swiss Federal Institute of Technology Lausanne (EPFL); Lausanne, Switzerland.
authors.forename: Anguraj
authors.initials: A
authors.lastname: Sadanandam
authors.affiliation: Cancer Research UK Cambridge Institute; University of Cambridge; Cambridge, UK.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory for Experimental Oncology and Radiobiology; Center for Experimental Molecular Medicine; Academic Medical Center (AMC); Amsterdam, The Netherlands.
authors.forename: Felipe
authors.initials: F
authors.lastname: de Sousa E Melo
authors.affiliation: Department of Biomedical Engineering; Oregon Health and Science University; Portland, OR USA.
authors.forename: Joe W
authors.initials: JW
authors.lastname: Gray
authors.affiliation: Cancer Research UK Cambridge Institute; University of Cambridge; Cambridge, UK; Laboratory for Experimental Oncology and Radiobiology; Center for Experimental Molecular Medicine; Academic Medical Center (AMC); Amsterdam, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Vermeulen
authors.affiliation: Swiss Institute for Experimental Cancer Research; Swiss Federal Institute of Technology Lausanne (EPFL); Lausanne, Switzerland.
authors.forename: Douglas
authors.initials: D
authors.lastname: Hanahan
authors.affiliation: Laboratory for Experimental Oncology and Radiobiology; Center for Experimental Molecular Medicine; Academic Medical Center (AMC); Amsterdam, The Netherlands.
authors.forename: Jan Paul
authors.initials: JP
authors.lastname: Medema
mesh_terms: D003110:Colonic Neoplasms / Q000145:classification* / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000628:therapy*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans
keywords: CIMP; MSI; cancer subtypes; cetuximab; colorectal cancer; consensus clustering; serrated pathway; therapy resistance