Journal article
Whole-genome landscape of pancreatic neuroendocrine tumours
A Scarpa, DK Chang, K Nones, V Corbo, AM Patch, P Bailey, RT Lawlor, AL Johns, DK Miller, A Mafficini, B Rusev, M Scardoni, D Antonello, S Barbi, KO Sikora, S Cingarlini, C Vicentini, S McKay, MCJ Quinn, TJC Bruxner Show all
Nature | NATURE PUBLISHING GROUP | Published : 2017
DOI: 10.1038/nature21063
Abstract
The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary PanNETs and defined the genomic events that characterize their pathogenesis. Here we describe the mutational signatures they harbour, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. Clinically sporadic PanNETs contain a larger-than-expected proportion of germline mutations, including previously unreported mutations in the DNA repair genes MUTYH, CHEK2 and BRCA2. Together with mutations in ..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank E. Missiaglia, S. Beghelli, N. Sperandio, G. Bonizzato, S. Grimaldi, F. Pisani, C. Cantu, G. Zamboni and P. Merlini for assistance at the ARC-Net Research Centre and Verona University; C. Axford, M.-A. Brancato, S. Rowe, M. Thomas, S. Simpson and G. Hammond for central coordination of the Australian Pancreatic Cancer Genome Initiative, data management and quality control; M. Martyn-Smith, L. Braatvedt, H. Tang, V. Papangelis and M. Beilin for biospecimen acquisition; D. Gwynne and D. Stetner for support at the Queensland Centre for Medical Genomics; and The Kinghorn Centre for Clinical Genomics for genome sequencing of validation samples. Funding support was from: Italian Ministry of Research (Cancer Genome Project FIRB RBAP10AHJB); Associazione Italiana Ricerca Cancro (AIRC n. 12182); Fondazione Italiana Malattie Pancreas - Ministero Salute (CUP_J33G13000210001); National Health and Medical Research Council of Australia (NHMRC; 631701, 535903, CDF 1112113, PRF 1025427, SRF 455857, 535903); The Queensland State Government Smart State National and International Research Alliances Program (NIRAP); Institute for Molecular Bioscience/University of Queensland; The Royal Australasian College of Physicians, Sidney Catalyst, NHMRC, Pancare Australia; Australian Government: Department of Innovation, Industry, Science and Research (DIISR); Australian Cancer Research Foundation (ACRF); Cancer Council NSW (SRP06-01, SRP11-01.ICGC); Cancer Institute NSW (10/ECF/2-26; 06/ECF/1-24; 09/CDF/2-40; 07/CDF/1-03; 10/CRF/1-01, 08/RSA/1-15, 07/CDF/1-28, 10/CDF/2-26,10/FRL/2-03, 06/RSA/1-05, 09/RIG/1-02, 10/TPG/1-04, 11/REG/1-10, 11/CDF/3-26); Garvan Institute of Medical Research; Avner Nahmani Pancreatic Cancer Research Foundation; R.T. Hall Trust; Petre Foundation; Philip Hemstritch Foundation; Gastroenterological Society of Australia (GESA Senior Research Fellowship); Royal Australasian College of Surgeons (RACS); Royal Australasian College of Physicians (RACP); Royal College of Pathologists of Australasia (RCPA); QIMR Berghofer Medical Research; The Keith Boden Fellowship (K.N.); NHGRI U54 HG003273; CPRIT grant RP101353-P7; Wellcome Trust Senior Investigator Award (103721/Z/14/Z); CRUK Programme (C29717/A17263 and C29717/A18484); CRUK Glasgow Centre (C596/A18076); CRUK Clinical Training Award (C596/A20921); Pancreatic Cancer UK Future Research Leaders Fund; The Howat Foundation; and the University of Glasgow.