Genomic characterization of a well-differentiated grade 3 pancreatic neuroendocrine tumor

Cold Spring Harb Mol Case Stud. 2019 Jun 3;5(3):a003814. doi: 10.1101/mcs.a003814. Print 2019 Jun.


Pancreatic neuroendocrine neoplasms (PanNENs) represent a minority of pancreatic neoplasms that exhibit variability in prognosis. Ongoing mutational analyses of PanNENs have found recurrent abnormalities in chromatin remodeling genes (e.g., DAXX and ATRX), and mTOR pathway genes (e.g., TSC2, PTEN PIK3CA, and MEN1), some of which have relevance to patients with related familial syndromes. Most recently, grade 3 PanNENs have been divided into two groups based on differentiation, creating a new group of well-differentiated grade 3 neuroendocrine tumors (PanNETs) that have had a limited whole-genome level characterization to date. In a patient with a metastatic well-differentiated grade 3 PanNET, our study utilized whole-genome sequencing of liver metastases for the comparative analysis and detection of single-nucleotide variants, insertions and deletions, structural variants, and copy-number variants, with their biologic relevance confirmed by RNA sequencing. We found that this tumor most notably exhibited a TSC1-disrupting fusion, showed a novel CHD7-BEND2 fusion, and lacked any somatic variants in ATRX, DAXX, and MEN1.

Trial registration: NCT02155621.

Keywords: neoplasm of the pancreas; neuroendocrine neoplasm.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy, Large-Core Needle
  • DNA Copy Number Variations*
  • DNA Helicases / genetics*
  • DNA-Binding Proteins / genetics*
  • Exome Sequencing
  • Gene Expression Profiling
  • Gene Fusion
  • Genomics*
  • Humans
  • Liver / pathology
  • Male
  • Neoplasm Metastasis
  • Neuroendocrine Tumors / classification
  • Neuroendocrine Tumors / genetics*
  • Neuroendocrine Tumors / pathology
  • Pancreas / pathology
  • Pancreatic Neoplasms / classification
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Tuberous Sclerosis Complex 1 Protein / genetics*


  • DNA-Binding Proteins
  • TSC1 protein, human
  • Tuberous Sclerosis Complex 1 Protein
  • DNA Helicases
  • CHD7 protein, human

Associated data


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