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

• Published in: Cold Spring Harbor molecular case studies Vol. 5; no. 3; p. a003814
• Main Authors: Williamson, Laura M, Steel, Michael, Grewal, Jasleen K, Thibodeau, My Lihn, Zhao, Eric Y, Loree, Jonathan M, Yang, Kevin C, Gorski, Sharon M, Mungall, Andrew J, Mungall, Karen L, Moore, Richard A, Marra, Marco A, Laskin, Janessa, Renouf, Daniel J, Schaeffer, David F, Jones, Steven J M
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.06.2019
• Subjects: Abnormalities; Adult; Biopsy, Large-Core Needle; Chromatin remodeling; Comparative analysis; Daxx protein; Disruption; DNA Copy Number Variations; DNA Helicases - genetics; DNA-Binding Proteins - genetics; Gene Expression Profiling; Gene Fusion; Gene sequencing; Genes; Genomes; Genomics; Humans; Liver - pathology; Male; Metastases; Neoplasm Metastasis; Neoplasms; Neuroendocrine tumors; Neuroendocrine Tumors - classification; Neuroendocrine Tumors - genetics; Neuroendocrine Tumors - pathology; Nucleotides; Pancreas; Pancreas - pathology; Pancreatic Neoplasms - classification; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Prognosis; PTEN protein; Ribonucleic acid; RNA; TOR protein; Tuberous Sclerosis Complex 1; Tuberous Sclerosis Complex 1 Protein - genetics; Tuberous Sclerosis Complex 2; Tumors; Whole Exome Sequencing; neoplasm of the pancreas; neuroendocrine neoplasm
• ISSN: 2373-2865; 2373-2873
• DOI: 10.1101/mcs.a003814

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., and ), and mTOR pathway genes (e.g., , , and ), 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 -disrupting fusion, showed a novel fusion, and lacked any somatic variants in , , and .