Authors

Michaël Noë, 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
Violeta Beleva Guthrie, Johns Hopkins University School of Medicine
Waki Hosoda, Johns Hopkins University School of Medicine
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 and Hospital Trust of Verona
Giovanni Butturini, Pederzoli Hospital
Giuseppe Zamboni, University of Verona
Paola Castelli, IRCCS Sacro Cuore Don Calabria Hospital
Seung-Mo Hong, University of Ulsan College of Medicine
Shinichi Yachida, Osaka University
Nobuyoshi Hiraoka, National Cancer Center Hospital
Anthony J Gill, University of Sydney
Jaswinder S Samra, Macquarie University
G Johan A Offerhaus, The University Medical Center Utrecht
Anne Hoorens, Ghent University Hospital
Joanne Verheij, Academic Medical Center
Casper Jansen, Laboratory for Pathology Eastern Netherlands
N Volkan Adsay, Koc University School of Medicine
Wei Jiang, Thomas Jefferson UniversityFollow
Jordan Winter, University Hospitals Cleveland Medical Center and Seidman Cancer Center
Jorge Albores-Saavedra, Medica Sur Clinic and Foundation
Benoit Terris, Université Paris Descartes
Elizabeth D Thompson, Johns Hopkins University School of Medicine
Nicholas J Roberts, Johns Hopkins University School of Medicine
Ralph H Hruban, Johns Hopkins University School of Medicine
Rachel Karchin, Johns Hopkins University School of Medicine
Robert B Scharpf, Johns Hopkins University School of Medicine
Lodewijk A A Brosens, Radboud University Medical Center
Victor E Velculescu, Johns Hopkins University School of Medicine
Laura D Wood, Johns Hopkins University School of Medicine

Document Type

Article

Publication Date

8-14-2020

Comments

This article is the author’s final published version in Nature Communications, Volume 11, Issue 1, August 2020, Article number 4085.

The published version is available at https://doi.org/10.1038/s41467-020-17917-8. Copyright © Noë et al.

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.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

32796935

Language

English

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