Genomic characterization of malignant progression in neoplastic pancreatic cysts

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, Antonio Pea, Aldo Scarpa, Giovanni Butturini, Giuseppe Zamboni, Paola Castelli, Seung Mo Hong, Shinichi Yachida, Nobuyoshi Hiraoka, Anthony J. GillJaswinder S. Samra, G. Johan A. Offerhaus, Anne Hoorens, Joanne Verheij, Casper Jansen, N. Volkan Adsay, Wei Jiang, Jordan Winter, Jorge Albores-Saavedra, Benoit Terris, Elizabeth D. Thompson, Nicholas J. Roberts, Ralph H. Hruban, Rachel Karchin, Robert B. Scharpf, Lodewijk A. A. Brosens, Victor E. Velculescu, Laura D. Wood*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)
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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.

Original languageEnglish
Article number4085
Pages (from-to)1-12
Number of pages12
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 14 Aug 2020

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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