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Type: Journal article
Title: Whole-genome landscape of pancreatic neuroendocrine tumours
Author: Scarpa, A.
Chang, D.
Nones, K.
Corbo, V.
Patch, A.
Bailey, P.
Lawlor, R.
Johns, A.
Miller, D.
Mafficini, A.
Rusev, B.
Scardoni, M.
Antonello, D.
Barbi, S.
Sikora, K.
Cingarlini, S.
Vicentini, C.
McKay, S.
Quinn, M.
Bruxner, T.
et al.
Citation: Nature, 2017; 543(7643):65-71
Publisher: Nature Publishing Group
Issue Date: 2017
ISSN: 0028-0836
Statement of
Aldo Scarpa … Andrea Mafficini … Davide Antonello … Suzanne McLean … Luca Landoni … Nam Q. Nguyen … et al.
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.
Keywords: Neuroendocrine cancer; cancer genomics
Rights: © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved
RMID: 0030065581
DOI: 10.1038/nature21063
Grant ID:
Appears in Collections:Medicine publications

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