- Title
- Whole-genome landscape of pancreatic neuroendocrine tumours
- Creator
- Scarpa, Aldo; Chang, David K.; Rusev, Borislav; Scardoni, Maria; Antonello, Davide; Barbi, Stefano; Sikora, Katarzyna O.; Cingarlini, Sara; Vicentini, Caterina; McKay, Skye; Quinn, Michael C. J.; Bruxner, Timothy J. C.; Nones, Katia; Scarlett, Christopher J.; Corbo, Vincenzo; Patch, Ann-Marie; Bailey, Peter; Lawlor, Rita T.; Johns, Amber L.; Miller, David K.; Mafficini, Andrea
- Relation
- Nature Vol. 543, Issue 7643, p. 65-+
- Publisher Link
- http://dx.doi.org/10.1038/nature21063
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2017
- Description
- 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.
- Subject
- pancreatic cancer; pancreatic neuroendocrine tumours; whole-genome sequencing; gene mutation; mutational signatures
- Identifier
- http://hdl.handle.net/1959.13/1399036
- Identifier
- uon:34522
- Identifier
- ISSN:0028-0836
- Language
- eng
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