Genomic characterization of malignant progression in neoplastic pancreatic cysts

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.

Recommended Citation

Noë, Michaël; Niknafs, Noushin; Fischer, Catherine G; Hackeng, Wenzel M; Beleva Guthrie, Violeta; Hosoda, Waki; Debeljak, Marija; Papp, Eniko; Adleff, Vilmos; White, James R; Luchini, Claudio; Pea, Antonio; Scarpa, Aldo; Butturini, Giovanni; Zamboni, Giuseppe; Castelli, Paola; Hong, Seung-Mo; Yachida, Shinichi; Hiraoka, Nobuyoshi; Gill, Anthony J; Samra, Jaswinder S; Offerhaus, G Johan A; Hoorens, Anne; Verheij, Joanne; Jansen, Casper; Adsay, N Volkan; Jiang, Wei; Winter, Jordan; Albores-Saavedra, Jorge; Terris, Benoit; Thompson, Elizabeth D; Roberts, Nicholas J; Hruban, Ralph H; Karchin, Rachel; Scharpf, Robert B; Brosens, Lodewijk A A; Velculescu, Victor E; and Wood, Laura D, "Genomic characterization of malignant progression in neoplastic pancreatic cysts" (2020). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 302.
https://jdc.jefferson.edu/pacbfp/302

Creative Commons License

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

PubMed ID

32796935

Language

English