{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T12:43:49Z","timestamp":1780663429703,"version":"3.54.1"},"reference-count":52,"publisher":"Cold Spring Harbor Laboratory","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:p>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., <jats:italic>DAXX<\/jats:italic> and <jats:italic>ATRX<\/jats:italic>), and mTOR pathway genes (e.g., <jats:italic>TSC2<\/jats:italic>, <jats:italic>PTEN PIK3CA<\/jats:italic>, and <jats:italic>MEN1<\/jats:italic>), 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 <jats:italic>TSC1<\/jats:italic>-disrupting fusion, showed a novel <jats:italic>CHD7\u2013BEND2<\/jats:italic> fusion, and lacked any somatic variants in <jats:italic>ATRX<\/jats:italic>, <jats:italic>DAXX<\/jats:italic>, and <jats:italic>MEN1<\/jats:italic>.<\/jats:p>","DOI":"10.1101\/mcs.a003814","type":"journal-article","created":{"date-parts":[[2019,6,3]],"date-time":"2019-06-03T18:45:26Z","timestamp":1559587526000},"page":"a003814","source":"Crossref","is-referenced-by-count":33,"title":["Genomic characterization of a well-differentiated grade 3 pancreatic neuroendocrine tumor"],"prefix":"10.1101","volume":"5","author":[{"given":"Laura M.","family":"Williamson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Steel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasleen K.","family":"Grewal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"My Lihn","family":"Thibodeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric Y.","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Loree","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C.","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon M.","family":"Gorski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Mungall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Mungall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco A.","family":"Marra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janessa","family":"Laskin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Renouf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Schaeffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.M.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2019,6,3]]},"reference":[{"key":"2021112406074614000_5.3.a003814.1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btn007"},{"key":"2021112406074614000_5.3.a003814.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.12.008"},{"key":"2021112406074614000_5.3.a003814.3","doi-asserted-by":"publisher","DOI":"10.1038\/nature08733"},{"key":"2021112406074614000_5.3.a003814.4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.34.15_suppl.4020"},{"key":"2021112406074614000_5.3.a003814.5","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp367"},{"key":"2021112406074614000_5.3.a003814.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1316158"},{"key":"2021112406074614000_5.3.a003814.7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C300226200"},{"key":"2021112406074614000_5.3.a003814.8","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2015-0476"},{"key":"2021112406074614000_5.3.a003814.9","doi-asserted-by":"publisher","DOI":"10.1101\/gad.213314.113"},{"key":"2021112406074614000_5.3.a003814.10","doi-asserted-by":"publisher","DOI":"10.1101\/gad.252122.114"},{"key":"2021112406074614000_5.3.a003814.11","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.0589"},{"key":"2021112406074614000_5.3.a003814.12","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr629"},{"key":"2021112406074614000_5.3.a003814.13","unstructured":"Edge S , Byrd DR , Compton CC , Fritz AG , Greene FL , Trotti A . 2010. 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