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. 2017 Mar 2;543(7643):65-71.
doi: 10.1038/nature21063. Epub 2017 Feb 15.

Whole-genome landscape of pancreatic neuroendocrine tumours

Aldo Scarpa  1   2 David K Chang  3   4   5   6   7 Katia Nones  8   9 Vincenzo Corbo  1   2 Ann-Marie Patch  8   9 Peter Bailey  3   9 Rita T Lawlor  1   2 Amber L Johns  5 David K Miller  9 Andrea Mafficini  1 Borislav Rusev  1 Maria Scardoni  2 Davide Antonello  10 Stefano Barbi  2 Katarzyna O Sikora  1 Sara Cingarlini  11 Caterina Vicentini  1 Skye McKay  5 Michael C J Quinn  8   9 Timothy J C Bruxner  9 Angelika N Christ  9 Ivon Harliwong  9 Senel Idrisoglu  9 Suzanne McLean  9 Craig Nourse  3   9 Ehsan Nourbakhsh  9 Peter J Wilson  9 Matthew J Anderson  9 J Lynn Fink  9 Felicity Newell  8   9 Nick Waddell  9 Oliver Holmes  8   9 Stephen H Kazakoff  8   9 Conrad Leonard  8   9 Scott Wood  8   9 Qinying Xu  8   9 Shivashankar Hiriyur Nagaraj  9 Eliana Amato  1   2 Irene Dalai  1   2 Samantha Bersani  2 Ivana Cataldo  1   2 Angelo P Dei Tos  12 Paola Capelli  2 Maria Vittoria Davì  13 Luca Landoni  10 Anna Malpaga  10 Marco Miotto  10 Vicki L J Whitehall  8   14   15 Barbara A Leggett  8   14   16 Janelle L Harris  8 Jonathan Harris  17 Marc D Jones  3 Jeremy Humphris  5 Lorraine A Chantrill  5 Venessa Chin  5 Adnan M Nagrial  5 Marina Pajic  5 Christopher J Scarlett  5   18 Andreia Pinho  5 Ilse Rooman  5 Christopher Toon  5 Jianmin Wu  5   19 Mark Pinese  5 Mark Cowley  5 Andrew Barbour  20 Amanda Mawson  5 Emily S Humphrey  5 Emily K Colvin  5 Angela Chou  5   21 Jessica A Lovell  5 Nigel B Jamieson  3   4   22 Fraser Duthie  3   23 Marie-Claude Gingras  24   25 William E Fisher  25 Rebecca A Dagg  26 Loretta M S Lau  26 Michael Lee  27 Hilda A Pickett  27 Roger R Reddel  27 Jaswinder S Samra  28   29 James G Kench  5   29   30 Neil D Merrett  6   31 Krishna Epari  32 Nam Q Nguyen  33 Nikolajs Zeps  34   35   36 Massimo Falconi  10 Michele Simbolo  1 Giovanni Butturini  10 George Van Buren  25 Stefano Partelli  10 Matteo Fassan  1 Australian Pancreatic Cancer Genome InitiativeKum Kum Khanna  8 Anthony J Gill  5   29 David A Wheeler  24 Richard A Gibbs  24 Elizabeth A Musgrove  3 Claudio Bassi  10 Giampaolo Tortora  11 Paolo Pederzoli  10 John V Pearson  8   9 Nicola Waddell  8   9 Andrew V Biankin  3   4   5   6   7 Sean M Grimmond  37
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Free article

Whole-genome landscape of pancreatic neuroendocrine tumours

Aldo Scarpa et al. Nature. .
Free article

Erratum in

  • Corrigendum: Whole-genome landscape of pancreatic neuroendocrine tumours.
    Scarpa A, Chang DK, Nones K, Corbo V, Patch AM, Bailey P, Lawlor RT, Johns AL, Miller DK, Mafficini A, Rusev B, Scardoni M, Antonello D, Barbi S, Sikora KO, Cingarlini S, Vicentini C, McKay S, Quinn MCJ, Bruxner TJC, Christ AN, Harliwong I, Idrisoglu S, McLean S, Nourse C, Nourbakhsh E, Wilson PJ, Anderson MJ, Fink JL, Newell F, Waddell N, Holmes O, Kazakoff SH, Leonard C, Wood S, Xu Q, Hiriyur Nagaraj S, Amato E, Dalai I, Bersani S, Cataldo I, Dei Tos AP, Capelli P, Vittoria Davì M, Landoni L, Malpaga A, Miotto M, Whitehall VLJ, Leggett BA, Harris JL, Harris J, Jones MD, Humphris J, Chantrill LA, Chin V, Nagrial AM, Pajic M, Scarlett CJ, Pinho A, Rooman I, Toon C, Wu J, Pinese M, Cowley M, Barbour A, Mawson A, Humphrey ES, Colvin EK, Chou A, Lovell JA, Jamieson NB, Duthie F, Gingras MC, Fisher WE, Dagg RA, Lau LMS, Lee M, Pickett HA, Reddel RR, Samra JS, Kench JG, Merrett ND, Epari K, Nguyen NQ, Zeps N, Falconi M, Simbolo M, Butturini G, Van Buren G, Partelli S, Fassan M; Australian Pancreatic Cancer Genome Initiative; Khanna KK, Gill AJ, Wheeler DA, Gibbs RA, Musgrove EA, Bassi C, Tortora G, Pederzoli P, Pearson JV, Waddell N, Biankin AV, Grimmond SM. Scarpa A, et al. Nature. 2017 Oct 26;550(7677):548. doi: 10.1038/nature24026. Epub 2017 Sep 27. Nature. 2017. PMID: 28953865

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.

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