{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T08:58:01Z","timestamp":1793177881587,"version":"4.5.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000147","name":"Canadian Cancer Society","doi-asserted-by":"publisher","award":["#707495"],"award-info":[{"award-number":["#707495"]}],"id":[{"id":"10.13039\/501100000147","id-type":"DOI","asserted-by":"publisher"}]},{"name":"2017 Neuroendocrine Tumor Research Foundation \u2013 AACR Grant","award":["#17-60-33-GORS"],"award-info":[{"award-number":["#17-60-33-GORS"]}]},{"DOI":"10.13039\/501100015803","name":"BC Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000233","name":"Genome British Columbia","doi-asserted-by":"publisher","award":["project B20POG"],"award-info":[{"award-number":["project B20POG"]}],"id":[{"id":"10.13039\/501100000233","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000245","name":"Michael Smith Health Research BC","doi-asserted-by":"publisher","award":["Professional Investigator Award"],"award-info":[{"award-number":["Professional Investigator Award"]}],"id":[{"id":"10.13039\/501100000245","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neuroendocrine neoplasms (NENs) encompass a highly heterogeneous group of neoplasms with varying prognoses and molecular alterations. Molecular profiling studies have furthered our understanding of NENs, but the majority of previous studies have focused on primary tumors and on mutational landscapes using DNA sequencing data. Here, we describe the genomic and transcriptomic landscapes of 28 metastatic NENs across different primary anatomical sites (PASs) and their potential clinical implications. Although our cohort is small, our analyses provide further insights on the molecular commonalities and distinctions between metastatic NENs of different PASs. Comparison to several reference transcriptome data sets revealed that despite considerable whole genome and transcriptome variability in NENs, the metastatic NENs are still more like each other than other cancer types. Our study also highlights the potential utility of NEN transcriptome data for molecular classification and clinical decision making.<\/jats:p>","DOI":"10.1038\/s41598-025-00549-7","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T02:48:54Z","timestamp":1746499734000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genomic and transcriptomic landscapes of metastatic neuroendocrine neoplasms from distinct primary sites and their clinical implications"],"prefix":"10.1038","volume":"15","author":[{"given":"Kathleen","family":"Wee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C.","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Schaeffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janessa","family":"Laskin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco A.","family":"Marra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Loree","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon M.","family":"Gorski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"549_CR1","doi-asserted-by":"publisher","first-page":"E398","DOI":"10.1503\/cmaj.160771","volume":"189","author":"MJ Raphael","year":"2017","unstructured":"Raphael, M. J., Chan, D. L., Law, C. & Singh, S. Principles of diagnosis and management of neuroendocrine tumours. CMAJ 189, E398\u2013E404 (2017).","journal-title":"CMAJ"},{"key":"549_CR2","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1111\/his.13975","volume":"76","author":"ID Nagtegaal","year":"2020","unstructured":"Nagtegaal, I. D. et al. The 2019 WHO classification of tumours of the digestive system. Histopathology 76, 182\u2013188 (2020).","journal-title":"Histopathology"},{"key":"549_CR3","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1038\/s41379-018-0110-y","volume":"31","author":"G Rindi","year":"2018","unstructured":"Rindi, G. et al. A common classification framework for neuroendocrine neoplasms: an international agency for research on cancer (IARC) and world health organization (WHO) expert consensus proposal. Mod. Pathol. 31, 1770\u20131786 (2018).","journal-title":"Mod. Pathol."},{"key":"549_CR4","doi-asserted-by":"publisher","first-page":"4612","DOI":"10.1038\/s41467-021-24812-3","volume":"12","author":"J van Riet","year":"2021","unstructured":"van Riet, J. et al. The genomic landscape of 85 advanced neuroendocrine neoplasms reveals subtype-heterogeneity and potential therapeutic targets. Nat. Commun. 12, 4612 (2021).","journal-title":"Nat. Commun."},{"key":"549_CR5","doi-asserted-by":"publisher","first-page":"a002329","DOI":"10.1101\/mcs.a002329","volume":"4","author":"HL Wong","year":"2018","unstructured":"Wong, H. L. et al. Molecular characterization of metastatic pancreatic neuroendocrine tumors (PNETs) using whole-genome and transcriptome sequencing. Mol. Case Stud. 4, a002329 (2018).","journal-title":"Mol. Case Stud."},{"key":"549_CR6","doi-asserted-by":"publisher","first-page":"a003814","DOI":"10.1101\/mcs.a003814","volume":"5","author":"LM Williamson","year":"2019","unstructured":"Williamson, L. M. et al. Genomic characterization of a well-differentiated grade 3 pancreatic neuroendocrine tumor. Mol. Case Stud. 5, a003814 (2019).","journal-title":"Mol. Case Stud."},{"key":"549_CR7","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/s43018-020-0050-6","volume":"1","author":"E Pleasance","year":"2020","unstructured":"Pleasance, E. et al. Pan-cancer analysis of advanced patient tumors reveals interactions between therapy and genomic landscapes. Nat. Cancer 1, 452\u2013468 (2020).","journal-title":"Nat. Cancer"},{"key":"549_CR8","doi-asserted-by":"publisher","first-page":"3518","DOI":"10.1038\/ncomms4518","volume":"5","author":"L Fernandez-Cuesta","year":"2014","unstructured":"Fernandez-Cuesta, L. et al. Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids. Nat. Commun. 5, 3518 (2014).","journal-title":"Nat. Commun."},{"key":"549_CR9","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/nature21063","volume":"543","author":"A Scarpa","year":"2017","unstructured":"Scarpa, A. et al. Whole-genome landscape of pancreatic neuroendocrine tumours. Nature 543, 65\u201371 (2017).","journal-title":"Nature"},{"key":"549_CR10","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1097\/PAS.0b013e3182417d36","volume":"36","author":"S Yachida","year":"2012","unstructured":"Yachida, S. et al. Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors. Am. J. Surg. Pathol. 36, 173\u2013184 (2012).","journal-title":"Am. J. Surg. Pathol."},{"key":"549_CR11","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nature14664","volume":"524","author":"J George","year":"2015","unstructured":"George, J. et al. Comprehensive genomic profiles of small cell lung cancer. Nature 524, 47\u201353 (2015).","journal-title":"Nature"},{"key":"549_CR12","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1158\/1078-0432.CCR-16-0355","volume":"23","author":"T Miyoshi","year":"2017","unstructured":"Miyoshi, T. et al. Genomic profiling of large-cell neuroendocrine carcinoma of the lung. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 23, 757\u2013765 (2017).","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"issue":"1","key":"549_CR13","doi-asserted-by":"publisher","first-page":"77","DOI":"10.6061\/clinics\/2012(Sup01)14","volume":"67","author":"SM Wagner","year":"2012","unstructured":"Wagner, S. M., Zhu, S., Nicolescu, A. C. & Mulligan, L. M. Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2. Clin. (Sao Paulo, Brazil) 67(1), 77\u201384 (2012).","journal-title":"Clin. (Sao Paulo, Brazil)"},{"key":"549_CR14","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.1038\/s41467-017-01967-6","volume":"8","author":"AS Farrell","year":"2017","unstructured":"Farrell, A. S. et al. MYC regulates ductal-neuroendocrine lineage plasticity in pancreatic ductal adenocarcinoma associated with poor outcome and chemoresistance. Nat. Commun. 8, 1728 (2017).","journal-title":"Nat. Commun."},{"key":"549_CR15","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1126\/science.1200609","volume":"331","author":"Y Jiao","year":"2011","unstructured":"Jiao, Y. et al. DAXX\/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 331, 1199\u20131203 (2011).","journal-title":"Science"},{"key":"549_CR16","doi-asserted-by":"publisher","first-page":"109817","DOI":"10.1016\/j.celrep.2021.109817","volume":"37","author":"K Yang","year":"2021","unstructured":"Yang, K. et al. Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms. Cell Rep. 37, 109817 (2021).","journal-title":"Cell Rep."},{"key":"549_CR17","doi-asserted-by":"publisher","first-page":"2810","DOI":"10.1038\/ncomms3810","volume":"4","author":"Y Cao","year":"2013","unstructured":"Cao, Y. et al. Whole exome sequencing of insulinoma reveals recurrent T372R mutations in YY1. Nat. Commun. 4, 2810 (2013).","journal-title":"Nat. Commun."},{"key":"549_CR18","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","volume":"578","author":"LB Alexandrov","year":"2020","unstructured":"Alexandrov, L. B. et al. The repertoire of mutational signatures in human cancer. Nature 578, 94\u2013101 (2020).","journal-title":"Nature"},{"key":"549_CR19","doi-asserted-by":"publisher","first-page":"4833","DOI":"10.1038\/sj.onc.1202848","volume":"18","author":"I Bongarzone","year":"1999","unstructured":"Bongarzone, I. et al. The Glu632-Leu633 deletion in cysteine rich domain of Ret induces constitutive dimerization and alters the processing of the receptor protein. Oncogene 18, 4833\u20134838 (1999).","journal-title":"Oncogene"},{"key":"549_CR20","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/s42003-020-01469-0","volume":"4","author":"V Lakis","year":"2021","unstructured":"Lakis, V. et al. DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association. Commun. Biol. 4, 155 (2021).","journal-title":"Commun. Biol."},{"key":"549_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-018-0058-3","author":"B Lawrence","year":"2018","unstructured":"Lawrence, B. et al. Recurrent loss of heterozygosity correlates with clinical outcome in pancreatic neuroendocrine cancer. NPJ Genom. Med. https:\/\/doi.org\/10.1038\/s41525-018-0058-3 (2018).","journal-title":"NPJ Genom. Med."},{"key":"549_CR22","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s13073-020-00730-9","volume":"12","author":"R Quevedo","year":"2020","unstructured":"Quevedo, R. et al. Centromeric cohesion failure invokes a conserved choreography of chromosomal mis-segregations in pancreatic neuroendocrine tumor. Genome Med. 12, 38 (2020).","journal-title":"Genome Med."},{"key":"549_CR23","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.3390\/cancers12061461","volume":"12","author":"G Boons","year":"2020","unstructured":"Boons, G. et al. PDX1 DNA methylation distinguishes two subtypes of pancreatic neuroendocrine neoplasms with a different prognosis. Cancers 12, 1461 (2020).","journal-title":"Cancers"},{"key":"549_CR24","doi-asserted-by":"publisher","DOI":"10.1200\/PO.17.00267","author":"N Raj","year":"2018","unstructured":"Raj, N. et al. Real-time genomic characterization of metastatic pancreatic neuroendocrine tumors has prognostic implications and identifies potential germline actionability. JCO Precis. Oncol. https:\/\/doi.org\/10.1200\/PO.17.00267 (2018).","journal-title":"JCO Precis. Oncol."},{"key":"549_CR25","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1530\/ERC-14-0410","volume":"22","author":"N Sahnane","year":"2015","unstructured":"Sahnane, N. et al. Microsatellite unstable gastrointestinal neuroendocrine carcinomas: a new clinicopathological entity. Endocr. Relat. Cancer 22, 35\u201345 (2015).","journal-title":"Endocr. Relat. Cancer"},{"key":"549_CR26","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1007\/s12022-020-09612-7","volume":"31","author":"C Fraune","year":"2020","unstructured":"Fraune, C. et al. Homogeneous MMR deficiency throughout the entire tumor mass occurs in a subset of colorectal neuroendocrine carcinomas. Endocr. Pathol. 31, 182\u2013189 (2020).","journal-title":"Endocr. Pathol."},{"key":"549_CR27","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1038\/s41379-021-00918-3","volume":"35","author":"M Jaffrelot","year":"2022","unstructured":"Jaffrelot, M. et al. An unusual phenotype occurs in 15% of mismatch repair-deficient tumors and is associated with non-colorectal cancers and genetic syndromes. Mod. Pathol. 35, 427\u2013437 (2022).","journal-title":"Mod. Pathol."},{"key":"549_CR28","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/s41588-018-0138-4","volume":"50","author":"MJ Alvarez","year":"2018","unstructured":"Alvarez, M. J. et al. A precision oncology approach to the pharmacological target mechanistic dependencies in neuroendocrine tumors. Nat. Genet. 50, 979\u2013989 (2018).","journal-title":"Nat. Genet."},{"key":"549_CR29","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1007\/s12022-020-09660-z","volume":"32","author":"S Uccella","year":"2021","unstructured":"Uccella, S. et al. Genomics of high-grade neuroendocrine neoplasms: well-differentiated neuroendocrine tumor with high-grade features (G3 NET) and neuroendocrine carcinomas (NEC) of various anatomic sites. Endocr. Pathol. 32, 192\u2013210 (2021).","journal-title":"Endocr. Pathol."},{"key":"549_CR30","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.ccell.2016.03.001","volume":"29","author":"JK Lee","year":"2016","unstructured":"Lee, J. K. et al. N-Myc drives neuroendocrine prostate cancer initiated from human prostate epithelial cells. Cancer Cell 29, 536\u2013547 (2016).","journal-title":"Cancer Cell"},{"key":"549_CR31","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s12943-019-0941-2","volume":"18","author":"Y Yin","year":"2019","unstructured":"Yin, Y. et al. N-Myc promotes therapeutic resistance development of neuroendocrine prostate cancer by differentially regulating miR-421\/ATM pathway. Mol. Cancer 18, 11 (2019).","journal-title":"Mol. Cancer"},{"key":"549_CR32","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1007\/s12022-021-09689-8","volume":"33","author":"R Maragliano","year":"2022","unstructured":"Maragliano, R. et al. Mixed neuroendocrine\/non-neuroendocrine neoplasm (MiNEN) of the ovary arising from endometriosis: molecular pathology analysis in support of a pathogenetic paradigm. Endocr. Pathol. 33, 400\u2013410 (2022).","journal-title":"Endocr. Pathol."},{"key":"549_CR33","doi-asserted-by":"publisher","first-page":"P939","DOI":"10.1016\/j.annonc.2022.05.522","volume":"33","author":"E Pleasance","year":"2022","unstructured":"Pleasance, E. et al. Whole-genome and transcriptome analysis enhances precision cancer treatment options. Ann. Oncol. 33, P939-949 (2022).","journal-title":"Ann. Oncol."},{"key":"549_CR34","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","volume":"26","author":"H Li","year":"2010","unstructured":"Li, H. & Durbin, R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26, 589\u2013595 (2010).","journal-title":"Bioinformatics"},{"key":"549_CR35","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1093\/bioinformatics\/bts271","volume":"28","author":"CT Saunders","year":"2012","unstructured":"Saunders, C. T. et al. Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs. Bioinformatics 28, 1811\u20131817 (2012).","journal-title":"Bioinformatics"},{"key":"549_CR36","doi-asserted-by":"publisher","first-page":"R82","DOI":"10.1186\/gb-2010-11-8-r82","volume":"11","author":"SJ Jones","year":"2010","unstructured":"Jones, S. J. et al. Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors. Genome Biol. 11, R82 (2010).","journal-title":"Genome Biol."},{"key":"549_CR37","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1101\/gr.137570.112","volume":"22","author":"G Ha","year":"2012","unstructured":"Ha, G. et al. Integrative analysis of genome-wide loss of heterozygosity and monoallelic expression at nucleotide resolution reveals disrupted pathways in triple-negative breast cancer. Genome Res. 22, 1995\u20132007 (2012).","journal-title":"Genome Res."},{"key":"549_CR38","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1101\/gr.089532.108","volume":"19","author":"JT Simpson","year":"2009","unstructured":"Simpson, J. T. et al. ABySS: a parallel assembler for short read sequence data. Genome Res. 19, 1117\u20131123 (2009).","journal-title":"Genome Res."},{"key":"549_CR39","doi-asserted-by":"publisher","first-page":"2872","DOI":"10.1093\/bioinformatics\/btp367","volume":"25","author":"I Birol","year":"2009","unstructured":"Birol, I. et al. De novo transcriptome assembly with ABySS. Bioinformatics 25, 2872\u20132877 (2009).","journal-title":"Bioinformatics"},{"key":"549_CR40","doi-asserted-by":"publisher","first-page":"D749","DOI":"10.1093\/nar\/gkt1196","volume":"42","author":"P Flicek","year":"2014","unstructured":"Flicek, P. et al. Ensembl 2014. Nucleic Acids Res. 42, D749-755 (2014).","journal-title":"Nucleic Acids Res."},{"key":"549_CR41","doi-asserted-by":"publisher","first-page":"80","DOI":"10.4161\/fly.19695","volume":"6","author":"P Cingolani","year":"2012","unstructured":"Cingolani, P. et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly (Austin) 6, 80\u201392 (2012).","journal-title":"Fly (Austin)"},{"key":"549_CR42","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15\u201321 (2013).","journal-title":"Bioinformatics"},{"key":"549_CR43","doi-asserted-by":"crossref","first-page":"D682","DOI":"10.1093\/nar\/gkz1138","volume":"48","author":"AD Yates","year":"2020","unstructured":"Yates, A. D. et al. Ensemble 2020. Nucleic Acids Res. 48, D682-688 (2020).","journal-title":"Nucleic Acids Res."},{"key":"549_CR44","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/1471-2105-12-323","volume":"12","author":"B Li","year":"2011","unstructured":"Li, B. & Dewey, C. N. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformat. 12, 323 (2011).","journal-title":"BMC Bioinformat."},{"key":"549_CR45","doi-asserted-by":"publisher","first-page":"1572","DOI":"10.1093\/bioinformatics\/btq170","volume":"26","author":"MD Wilkerson","year":"2010","unstructured":"Wilkerson, M. D. & Hayes, D. N. ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics 26, 1572\u20131573 (2010).","journal-title":"Bioinformatics"},{"key":"549_CR46","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1093\/bioinformatics\/btt755","volume":"30","author":"B Niu","year":"2014","unstructured":"Niu, B. et al. MSIsensor: microsatellite instability detection using paired tumor-normal sequence data. Bioinformatics 30, 1015\u20131016 (2014).","journal-title":"Bioinformatics"},{"key":"549_CR47","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139\u2013140 (2010).","journal-title":"Bioinformatics"},{"key":"549_CR48","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","volume":"1","author":"A Liberzon","year":"2015","unstructured":"Liberzon, A. et al. The molecular signatures database hallmark gene set collection. Cell Syst. 1, 417\u2013425 (2015).","journal-title":"Cell Syst."},{"key":"549_CR49","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1038\/ng.3593","volume":"48","author":"MJ Alvarez","year":"2016","unstructured":"Alvarez, M. J. et al. Functional characterization of somatic mutations in cancer using network-based inference of protein activity. Nat. Genet. 48, 838\u2013847 (2016).","journal-title":"Nat. Genet."},{"key":"549_CR50","doi-asserted-by":"publisher","first-page":"2502","DOI":"10.1172\/JCI67963","volume":"123","author":"MS Banck","year":"2013","unstructured":"Banck, M. S. et al. The genomic landscape of small intestine neuroendocrine tumors. J. Clin. Investig. 123, 2502\u20132508 (2013).","journal-title":"J. Clin. Investig."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-00549-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-00549-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-00549-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T04:03:01Z","timestamp":1746504181000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-00549-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,6]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["549"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-00549-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,6]]},"assertion":[{"value":"9 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"DFS declares consultancy work outside of the submitted work from Alimentiv, Pfizer, Merck, Diaceutics, Astellas, Bayer; and Stock Ownership in Satisfai Health Inc.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This work was approved by and conducted in accordance with guidelines and regulations of the University of British Columbia\u2014BC Cancer Research Ethics Board and harmonized with Simon Fraser University Research Ethics Board (H16-01577). The cohort of 28 patients gave informed consent and enrolled in the POG program registered under clinical trial number NCT02155621.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"15770"}}