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Genomic characterization of malignant progression in neoplastic pancreatic cysts

Author

Listed:
  • Michaël Noë

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Noushin Niknafs

    (Johns Hopkins University School of Medicine)

  • Catherine G. Fischer

    (Johns Hopkins University School of Medicine)

  • Wenzel M. Hackeng

    (Johns Hopkins University School of Medicine
    The University Medical Center Utrecht)

  • Violeta Beleva Guthrie

    (Johns Hopkins University
    Johns Hopkins University)

  • Waki Hosoda

    (Johns Hopkins University School of Medicine
    Department of Pathology and Molecular Diagnostics, Aichi Cancer Center)

  • Marija Debeljak

    (Johns Hopkins University School of Medicine)

  • Eniko Papp

    (Johns Hopkins University School of Medicine)

  • Vilmos Adleff

    (Johns Hopkins University School of Medicine)

  • James R. White

    (Johns Hopkins University School of Medicine)

  • Claudio Luchini

    (University of Verona)

  • Antonio Pea

    (University and Hospital Trust of Verona)

  • Aldo Scarpa

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

  • Giovanni Butturini

    (Pederzoli Hospital)

  • Giuseppe Zamboni

    (University of Verona
    Pathology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar)

  • Paola Castelli

    (Pathology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar)

  • Seung-Mo Hong

    (Johns Hopkins University School of Medicine
    University of Ulsan College of Medicine)

  • Shinichi Yachida

    (Graduate School of Medicine, Osaka University)

  • Nobuyoshi Hiraoka

    (National Cancer Center Hospital)

  • Anthony J. Gill

    (University of Sydney
    Royal North Shore Hospital
    Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, Royal North Shore Hospital)

  • Jaswinder S. Samra

    (University of Sydney
    Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital
    Faculty of Medical and Health Sciences, Macquarie University)

  • G. Johan A. Offerhaus

    (The University Medical Center Utrecht)

  • Anne Hoorens

    (Ghent University Hospital)

  • Joanne Verheij

    (Academic Medical Center)

  • Casper Jansen

    (LABPON, Laboratory for Pathology Eastern Netherlands)

  • N. Volkan Adsay

    (Koc University School of Medicine)

  • Wei Jiang

    (Thomas Jefferson University)

  • Jordan Winter

    (University Hospitals Cleveland Medical Center and Seidman Cancer Center
    Case Comprehensive Cancer Center)

  • Jorge Albores-Saavedra

    (Medica Sur Clinic and Foundation)

  • Benoit Terris

    (Service de Pathologie, AP-HP, Hôpital Cochin, Université Paris Descartes)

  • Elizabeth D. Thompson

    (Johns Hopkins University School of Medicine)

  • Nicholas J. Roberts

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Ralph H. Hruban

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Rachel Karchin

    (Johns Hopkins University School of Medicine
    Johns Hopkins University
    Johns Hopkins University)

  • Robert B. Scharpf

    (Johns Hopkins University School of Medicine)

  • Lodewijk A. A. Brosens

    (The University Medical Center Utrecht
    Radboud University Medical Center)

  • Victor E. Velculescu

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine
    Johns Hopkins University)

  • Laura D. Wood

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

Abstract

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three years between the development of high-grade dysplasia and pancreatic cancer. Taken together, these data establish non-invasive IPMNs and MCNs as origins of invasive pancreatic cancer, identifying potential drivers of invasion, highlighting the complex clonal dynamics prior to malignant transformation, and providing opportunities for early detection and intervention.

Suggested Citation

  • Michaël Noë & Noushin Niknafs & Catherine G. Fischer & Wenzel M. Hackeng & Violeta Beleva Guthrie & Waki Hosoda & Marija Debeljak & Eniko Papp & Vilmos Adleff & James R. White & Claudio Luchini & Anto, 2020. "Genomic characterization of malignant progression in neoplastic pancreatic cysts," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17917-8
    DOI: 10.1038/s41467-020-17917-8
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