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Genomic analyses identify molecular subtypes of pancreatic cancer

Author

Listed:
  • Peter Bailey

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate)

  • David K. Chang

    (Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate
    The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research
    Bankstown Hospital
    South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales)

  • Katia Nones

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Amber L. Johns

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Ann-Marie Patch

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Marie-Claude Gingras

    (Human Genome Sequencing Center, Baylor College of Medicine
    Baylor College of Medicine
    Dan L. Duncan Cancer Center, Baylor College of Medicine)

  • David K. Miller

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Angelika N. Christ

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland)

  • Tim J. C. Bruxner

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland)

  • Michael C. Quinn

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Craig Nourse

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate)

  • L. Charles Murtaugh

    (University of Utah)

  • Ivon Harliwong

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland)

  • Senel Idrisoglu

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland)

  • Suzanne Manning

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland)

  • Ehsan Nourbakhsh

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland)

  • Shivangi Wani

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Lynn Fink

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland)

  • Oliver Holmes

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Venessa Chin

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Matthew J. Anderson

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland)

  • Stephen Kazakoff

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Conrad Leonard

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Felicity Newell

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland)

  • Nick Waddell

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland)

  • Scott Wood

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Qinying Xu

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Peter J. Wilson

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland)

  • Nicole Cloonan

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Karin S. Kassahn

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    Genetic and Molecular Pathology, SA Pathology
    School of Biological Sciences, The University of Adelaide)

  • Darrin Taylor

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland)

  • Kelly Quek

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland)

  • Alan Robertson

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland)

  • Lorena Pantano

    (Harvard Chan Bioinformatics Core, Harvard T. H. Chan School of Public Health)

  • Laura Mincarelli

    (Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate)

  • Luis N. Sanchez

    (Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate)

  • Lisa Evers

    (Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate)

  • Jianmin Wu

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Mark Pinese

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Mark J. Cowley

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Marc D. Jones

    (Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate
    The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Emily K. Colvin

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Adnan M. Nagrial

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Emily S. Humphrey

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Lorraine A. Chantrill

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research
    Macarthur Cancer Therapy Centre, Campbelltown Hospital)

  • Amanda Mawson

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Jeremy Humphris

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Angela Chou

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research
    St Vincent’s Hospital)

  • Marina Pajic

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research
    St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, New South Wales 2052)

  • Christopher J. Scarlett

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research
    School of Environmental & Life Sciences, University of Newcastle)

  • Andreia V. Pinho

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Marc Giry-Laterriere

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Ilse Rooman

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Jaswinder S. Samra

    (Royal North Shore Hospital, St Leonards
    University of Sydney)

  • James G. Kench

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research
    University of Sydney
    Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital)

  • Jessica A. Lovell

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Neil D. Merrett

    (South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales
    School of Medicine, University of Western Sydney)

  • Christopher W. Toon

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • Krishna Epari

    (Fiona Stanley Hospital)

  • Nam Q. Nguyen

    (Royal Adelaide Hospital)

  • Andrew Barbour

    (Princess Alexandra Hospital)

  • Nikolajs Zeps

    (School of Surgery M507, University of Western Australia, 35 Stirling Hwy, Nedlands 6009, Australia and St John of God Pathology)

  • Kim Moran-Jones

    (Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate)

  • Nigel B. Jamieson

    (Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate
    Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow
    West of Scotland Pancreatic Unit)

  • Janet S. Graham

    (Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate
    Beatson West of Scotland Cancer Centre)

  • Fraser Duthie

    (Southern General Hospital)

  • Karin Oien

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research
    Southern General Hospital)

  • Jane Hair

    (GGC Bio-repository, Southern General Hospital)

  • Robert Grützmann

    (Department of Surgery
    † Present address: Universitätsklinikum Erlangen, Department of Surgery, 91054 Erlangen, Germany.)

  • Anirban Maitra

    (UT MD Anderson Cancer Center)

  • Christine A. Iacobuzio-Donahue

    (Memorial Sloan Kettering Cancer Center)

  • Christopher L. Wolfgang

    (The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine
    The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine)

  • Richard A. Morgan

    (The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine)

  • Rita T. Lawlor

    (ARC-Net Applied Research on Cancer Centre, University and Hospital Trust of Verona
    University of Verona)

  • Vincenzo Corbo

    (ARC-Net Applied Research on Cancer Centre, University and Hospital Trust of Verona)

  • Claudio Bassi

    (Pancreas Institute, University and Hospital Trust of Verona)

  • Borislav Rusev

    (ARC-Net Applied Research on Cancer Centre, University and Hospital Trust of Verona)

  • Paola Capelli

    (University of Verona)

  • Roberto Salvia

    (Pancreas Institute, University and Hospital Trust of Verona)

  • Giampaolo Tortora

    (Comprehensive Cancer Centre, University and Hospital Trust of Verona)

  • Debabrata Mukhopadhyay

    (Mayo Clinic)

  • Gloria M. Petersen

    (Mayo Clinic)

  • Donna M. Munzy

    (Human Genome Sequencing Center, Baylor College of Medicine
    Baylor College of Medicine)

  • William E. Fisher

    (Elkins Pancreas Center, Baylor College of Medicine)

  • Saadia A. Karim

    (Cancer Research UK Beatson Institute)

  • James R. Eshleman

    (The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine)

  • Ralph H. Hruban

    (The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine)

  • Christian Pilarsky

    (Department of Surgery)

  • Jennifer P. Morton

    (Cancer Research UK Beatson Institute)

  • Owen J. Sansom

    (Cancer Research UK Beatson Institute
    Institute for Cancer Science, University of Glasgow)

  • Aldo Scarpa

    (ARC-Net Applied Research on Cancer Centre, University and Hospital Trust of Verona
    University of Verona)

  • Elizabeth A. Musgrove

    (Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate)

  • Ulla-Maja Hagbo Bailey

    (Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate)

  • Oliver Hofmann

    (Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate
    Harvard Chan Bioinformatics Core, Harvard T. H. Chan School of Public Health)

  • Robert L. Sutherland

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research)

  • David A. Wheeler

    (Human Genome Sequencing Center, Baylor College of Medicine
    Baylor College of Medicine)

  • Anthony J. Gill

    (The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research
    University of Sydney)

  • Richard A. Gibbs

    (Human Genome Sequencing Center, Baylor College of Medicine
    Baylor College of Medicine)

  • John V. Pearson

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Nicola Waddell

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Andrew V. Biankin

    (Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate
    The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research
    Bankstown Hospital
    South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales)

  • Sean M. Grimmond

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
    Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate
    University of Melbourne)

Abstract

Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

Suggested Citation

  • Peter Bailey & David K. Chang & Katia Nones & Amber L. Johns & Ann-Marie Patch & Marie-Claude Gingras & David K. Miller & Angelika N. Christ & Tim J. C. Bruxner & Michael C. Quinn & Craig Nourse & L. , 2016. "Genomic analyses identify molecular subtypes of pancreatic cancer," Nature, Nature, vol. 531(7592), pages 47-52, March.
    • Handle: RePEc:nat:nature:v:531:y:2016:i:7592:d:10.1038_nature16965
    DOI: 10.1038/nature16965
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