Whole-genome landscape of pancreatic neuroendocrine tumours

Article

关键词: EWING SARCOMA;    MUTATIONAL PROCESSES;    MOLECULAR SUBTYPES;    TP53 MUTATIONS;    PATHWAY GENES;    MTOR PATHWAY;    CANCER;    PROTEIN;    TRANSLOCATION;    SUPPRESSOR;   

DOI  :  10.1038/nature21063

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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