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Reconciliation of classification systems defining molecular subtypes of colorectal cancer
Authors:Anguraj Sadanandam  Xin Wang  Felipe de Sousa E Melo  Joe W Gray  Douglas Hanahan
Institution:1. Swiss Institute of Bioinformatics;2. Lausanne, Switzerland;3. Swiss Institute for Experimental Cancer Research;4. Swiss Federal Institute of Technology Lausanne (EPFL);5. Cancer Research UK Cambridge Institute;6. University of Cambridge;7. Cambridge, UK;8. Laboratory for Experimental Oncology and Radiobiology;9. Center for Experimental Molecular Medicine;10. Academic Medical Center (AMC);11. Amsterdam, The Netherlands;12. Department of Biomedical Engineering;13. Oregon Health and Science University;14. Portland, OR USA;15. Swiss Institute for Experimental Cancer Research
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.
Keywords:colorectal cancer  cancer subtypes  consensus clustering  therapy resistance  MSI  CIMP  cetuximab  serrated pathway
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