Document Type
Article
Publication Date
8-14-2020
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
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.