| Literature DB >> 28199314 |
Aldo Scarpa1,2, David K Chang3,4,5,6,7, Katia Nones8,9, Vincenzo Corbo1,2, Ann-Marie Patch8,9, Peter Bailey3,9, Rita T Lawlor1,2, Amber L Johns5, David K Miller9, Andrea Mafficini1, Borislav Rusev1, Maria Scardoni2, Davide Antonello10, Stefano Barbi2, Katarzyna O Sikora1, Sara Cingarlini11, Caterina Vicentini1, Skye McKay5, Michael C J Quinn8,9, Timothy J C Bruxner9, Angelika N Christ9, Ivon Harliwong9, Senel Idrisoglu9, Suzanne McLean9, Craig Nourse3,9, Ehsan Nourbakhsh9, Peter J Wilson9, Matthew J Anderson9, J Lynn Fink9, Felicity Newell8,9, Nick Waddell9, Oliver Holmes8,9, Stephen H Kazakoff8,9, Conrad Leonard8,9, Scott Wood8,9, Qinying Xu8,9, Shivashankar Hiriyur Nagaraj9, Eliana Amato1,2, Irene Dalai1,2, Samantha Bersani2, Ivana Cataldo1,2, Angelo P Dei Tos12, Paola Capelli2, Maria Vittoria Davì13, Luca Landoni10, Anna Malpaga10, Marco Miotto10, Vicki L J Whitehall8,14,15, Barbara A Leggett8,14,16, Janelle L Harris8, Jonathan Harris17, Marc D Jones3, Jeremy Humphris5, Lorraine A Chantrill5, Venessa Chin5, Adnan M Nagrial5, Marina Pajic5, Christopher J Scarlett5,18, Andreia Pinho5, Ilse Rooman5, Christopher Toon5, Jianmin Wu5,19, Mark Pinese5, Mark Cowley5, Andrew Barbour20, Amanda Mawson5, Emily S Humphrey5, Emily K Colvin5, Angela Chou5,21, Jessica A Lovell5, Nigel B Jamieson3,4,22, Fraser Duthie3,23, Marie-Claude Gingras24,25, William E Fisher25, Rebecca A Dagg26, Loretta M S Lau26, Michael Lee27, Hilda A Pickett27, Roger R Reddel27, Jaswinder S Samra28,29, James G Kench5,29,30, Neil D Merrett6,31, Krishna Epari32, Nam Q Nguyen33, Nikolajs Zeps34,35,36, Massimo Falconi10, Michele Simbolo1, Giovanni Butturini10, George Van Buren25, Stefano Partelli10, Matteo Fassan1, Kum Kum Khanna8, Anthony J Gill5,29, David A Wheeler24, Richard A Gibbs24, Elizabeth A Musgrove3, Claudio Bassi10, Giampaolo Tortora11, Paolo Pederzoli10, John V Pearson8,9, Nicola Waddell8,9, Andrew V Biankin3,4,5,6,7, Sean M Grimmond37.
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 MEN1 and VHL, these mutations occur in 17% of patients. Somatic mutations, including point mutations and gene fusions, were commonly found in genes involved in four main pathways: chromatin remodelling, DNA damage repair, activation of mTOR signalling (including previously undescribed EWSR1 gene fusions), and telomere maintenance. In addition, our gene expression analyses identified a subgroup of tumours associated with hypoxia and HIF signalling.Entities:
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Year: 2017 PMID： 28199314 DOI： 10.1038/nature21063
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962