title: Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin.
abstract: Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies.
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hoadley
authors.affiliation: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Yau
authors.affiliation: Department of Laboratory Medicine, University of California San Francisco, 2340 Sutter St, San Francisco, CA, 94115, USA.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Wolf
authors.affiliation: The Eli and Edythe Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cherniack
authors.affiliation: Research Unit on Biomedical Informatics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Dr. Aiguader 88, Barcelona 08003, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Tamborero
authors.affiliation: Department of Biomolecular Engineering, Center for Biomolecular Sciences and Engineering, University of California, Santa Cruz, 1156 High St., Santa Cruz, CA 95064, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Ng
authors.affiliation: Department of Computer Science and Center for Computational Molecular Biology, Brown University, 115 Waterman St, Providence RI 02912, USA.
authors.forename: Max D M
authors.initials: MDM
authors.lastname: Leiserson
authors.affiliation: The Genome Institute, Washington University, St Louis, MO 63108, USA.
authors.forename: Beifang
authors.initials: B
authors.lastname: Niu
authors.affiliation: The Genome Institute, Washington University, St Louis, MO 63108, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: McLellan
authors.affiliation: Department of Biomolecular Engineering, Center for Biomolecular Sciences and Engineering, University of California, Santa Cruz, 1156 High St., Santa Cruz, CA 95064, USA.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Uzunangelov
authors.affiliation: National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Jiashan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Genome Institute, Washington University, St Louis, MO 63108, USA.
authors.forename: Cyriac
authors.initials: C
authors.lastname: Kandoth
authors.affiliation: UT MD Anderson Cancer Center, Bioinformatics and Computational Biology, 1400 Pressler Street, Unit 1410, Houston, TX 77030, USA.
authors.forename: Rehan
authors.initials: R
authors.lastname: Akbani
authors.affiliation: USC Epigenome Center, University of Southern California Keck School of Medicine, 1450 Biggy Street, Los Angeles, CA 90033, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: Sage Bionetworks 1100 Fairview Avenue North, M1-C108, Seattle, WA 98109-1024, USA.
authors.forename: Larsson
authors.initials: L
authors.lastname: Omberg
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
authors.forename: Andy
authors.initials: A
authors.lastname: Chu
authors.affiliation: Sage Bionetworks 1100 Fairview Avenue North, M1-C108, Seattle, WA 98109-1024, USA.
authors.forename: Adam A
authors.initials: AA
authors.lastname: Margolin
authors.affiliation: Department of Laboratory Medicine, University of California San Francisco, 2340 Sutter St, San Francisco, CA, 94115, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Van't Veer
authors.affiliation: Research Unit on Biomedical Informatics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Dr. Aiguader 88, Barcelona 08003, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluís Companys, 23, Barcelona 08010, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Lopez-Bigas
authors.affiliation: USC Epigenome Center, University of Southern California Keck School of Medicine, 1450 Biggy Street, Los Angeles, CA 90033, USA.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Laird
authors.affiliation: Department of Computer Science and Center for Computational Molecular Biology, Brown University, 115 Waterman St, Providence RI 02912, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Raphael
authors.affiliation: The Genome Institute, Washington University, St Louis, MO 63108, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
authors.forename: A Gordon
authors.initials: AG
authors.lastname: Robertson
authors.affiliation: UT MD Anderson Cancer Center, Bioinformatics and Computational Biology, 1400 Pressler Street, Unit 1410, Houston, TX 77030, USA.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Byers
authors.affiliation: UT MD Anderson Cancer Center, Bioinformatics and Computational Biology, 1400 Pressler Street, Unit 1410, Houston, TX 77030, USA.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.affiliation: UT MD Anderson Cancer Center, Bioinformatics and Computational Biology, 1400 Pressler Street, Unit 1410, Houston, TX 77030, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Weinstein
authors.affiliation: Building 10, Room 4-2732, NIDCD/NIH, 10 Center Drive, Bethesda, MD 20892.
authors.forename: Carter
authors.initials: C
authors.lastname: Van Waes
authors.affiliation: Head and Neck Surgery Branch, NIDCD/NIH, 10 Center Drive, Room 5D55, Bethesda, MD 20892.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Medicine, University of California San Francisco, 450 35d St, San Francisco, CA, 94148, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Collisson
authors.affiliation: Buck Institute for Research on Aging, Novato, CA 94945, USA. Electronic address: cbenz@buckinstitute.org.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Benz
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA. Electronic address: cperou@med.unc.edu.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.affiliation: Department of Biomolecular Engineering, Center for Biomolecular Sciences and Engineering, University of California, Santa Cruz, 1156 High St., Santa Cruz, CA 95064, USA. Electronic address: jstuart@ucsc.edu.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Stuart
mesh_terms: D016000:Cluster Analysis; D006801:Humans; D009369:Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D059467:Transcriptome
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