GRCh38 · COSMIC v94

Summary

This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

Reference
Genomic characterization of malignant progression in neoplastic pancreatic cysts.
Paper ID
COSP48517
Authors
Noë M, Niknafs N, Fischer CG, Hackeng WM, Beleva Guthrie V, Hosoda W, Debeljak M, Papp E, Adleff V, White JR, Luchini C, Pea A, Scarpa A, Butturini G, Zamboni G, Castelli P, Hong SM, Yachida S, Hiraoka N, Gill AJ, Samra JS, Offerhaus GJA, Hoorens A, Verheij J, Jansen C, Adsay NV, Jiang W, Winter J, Albores-Saavedra J, Terris B, Thompson ED, Roberts NJ, Hruban RH, Karchin R, Scharpf RB, Brosens LAA, Velculescu VE and Wood LD
Affiliation
Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Journal
Nature communications, 2020;11(1):4085
ISSN: 2041-1723
PMID: 32796935 (view at PubMed or Europe PMC)
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.
Paper Status
Curated