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

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

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Canada's Michael Smith Genome Science Centre, BC Cancer, Vancouver, British Columbia V5Z 4S6, Canada.
Department of Pathology & Laboratory Medicine, Vancouver General Hospital, Vancouver, British Columbia V6T 2B5, Canada.
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6H 3N1, Canada.
Division of Medical Oncology, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada.
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
Pancreas Centre BC, Vancouver, British Columbia V5Z 1M9, Canada.
Contributed equally


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.



neoplasm of the pancreas; neuroendocrine neoplasm

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