whole-genome landscape of pancreatic neuroendocrine tumours.
2017-03-13
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:c65>65t:a base excision repair due to inactivation of , 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 , and . together with mutations in and , 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 gene fusions), and telomere maintenance. in addition, our gene expression analyses identified a subgroup of tumours associated with hypoxia and hif signalling.
