Genomic characterization of a well-differentiated grade 3 pancreatic neuroendocrine tumor
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 whi...
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Published in | Cold Spring Harbor molecular case studies Vol. 5; no. 3; p. a003814 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Cold Spring Harbor Laboratory Press
01.06.2019
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Abstract | 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
. |
---|---|
AbstractList | 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
. 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 . 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. |
Author | Steel, Michael Jones, Steven J M Thibodeau, My Lihn Schaeffer, David F Moore, Richard A Williamson, Laura M Grewal, Jasleen K Marra, Marco A Gorski, Sharon M Mungall, Andrew J Laskin, Janessa Mungall, Karen L Loree, Jonathan M Yang, Kevin C Zhao, Eric Y Renouf, Daniel J |
AuthorAffiliation | 4 Division of Medical Oncology, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada 1 Canada's Michael Smith Genome Science Centre, BC Cancer, Vancouver, British Columbia V5Z 4S6, Canada 2 Department of Pathology & Laboratory Medicine, Vancouver General Hospital, Vancouver, British Columbia V6T 2B5, Canada 3 Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6H 3N1, Canada 6 Pancreas Centre BC, Vancouver, British Columbia V5Z 1M9, Canada 5 Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada |
AuthorAffiliation_xml | – name: 6 Pancreas Centre BC, Vancouver, British Columbia V5Z 1M9, Canada – name: 2 Department of Pathology & Laboratory Medicine, Vancouver General Hospital, Vancouver, British Columbia V6T 2B5, Canada – name: 5 Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada – name: 1 Canada's Michael Smith Genome Science Centre, BC Cancer, Vancouver, British Columbia V5Z 4S6, Canada – name: 3 Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6H 3N1, Canada – name: 4 Division of Medical Oncology, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada |
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Keywords | neoplasm of the pancreas neuroendocrine neoplasm |
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Snippet | Pancreatic neuroendocrine neoplasms (PanNENs) represent a minority of pancreatic neoplasms that exhibit variability in prognosis. Ongoing mutational analyses... |
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SubjectTerms | 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 |
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Title | Genomic characterization of a well-differentiated grade 3 pancreatic neuroendocrine tumor |
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