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|Title:||Whole-genome landscape of pancreatic neuroendocrine tumours|
|Citation:||Nature, 2017; 543(7643):65-71|
|Publisher:||Nature Publishing Group|
|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|
|Appears in Collections:||Medicine publications|
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