{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:25:28Z","timestamp":1772252728067,"version":"3.50.1"},"reference-count":78,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T00:00:00Z","timestamp":1610150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005567","name":"H. Lee Moffitt Cancer Center and Research Institute","doi-asserted-by":"publisher","award":["P30-CA76292"],"award-info":[{"award-number":["P30-CA76292"]}],"id":[{"id":"10.13039\/100005567","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Moffitt Skin Cancer SPORE","award":["5P50CA168536-05"],"award-info":[{"award-number":["5P50CA168536-05"]}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["R1113"],"award-info":[{"award-number":["R1113"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["R1112"],"award-info":[{"award-number":["R1112"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>A central challenge in cancer genomics is the systematic identification of single and cooperating tumor suppressor gene mutations driving cellular transformation and tumor progression in the absence of oncogenic driver mutation(s). Multiple in vitro and in vivo gene inactivation screens have enhanced our understanding of the tumor suppressor gene landscape in various cancers. However, these studies are limited to single or combination gene effects, specific organs, or require sensitizing mutations. In this study, we developed and utilized a Sleeping Beauty transposon mutagenesis system that functions only as a gene trap to exclusively inactivate tumor suppressor genes. Using whole body transposon mobilization in wild type mice, we observed that cumulative gene inactivation can drive tumorigenesis of solid cancers. We provide a quantitative landscape of the tumor suppressor genes inactivated in these cancers and show that, despite the absence of oncogenic drivers, these genes converge on key biological pathways and processes associated with cancer hallmarks.<\/jats:p>","DOI":"10.3390\/cancers13020225","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T19:55:56Z","timestamp":1610308556000},"page":"225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Promoterless Transposon Mutagenesis Drives Solid Cancers via Tumor Suppressor Inactivation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5920-1929","authenticated-orcid":false,"given":"Aziz","family":"Aiderus","sequence":"first","affiliation":[{"name":"Department of Molecular Oncology, Moffitt Cancer Center &amp; Research Institute, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4324-9610","authenticated-orcid":false,"given":"Ana M.","family":"Contreras-Sandoval","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Moffitt Cancer Center &amp; Research Institute, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda L.","family":"Meshey","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Moffitt Cancer Center &amp; Research Institute, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin Y.","family":"Newberg","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Moffitt Cancer Center &amp; Research Institute, Tampa, FL 33612, USA"},{"name":"Cancer Research Program, Houston Methodist Research Institute, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerrold M.","family":"Ward","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah A.","family":"Swing","sequence":"additional","affiliation":[{"name":"Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neal G.","family":"Copeland","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore"},{"name":"Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy A.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore"},{"name":"Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7161-4523","authenticated-orcid":false,"given":"Karen M.","family":"Mann","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Moffitt Cancer Center &amp; Research Institute, Tampa, FL 33612, USA"},{"name":"Cancer Research Program, Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore"},{"name":"Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"},{"name":"Departments of Gastrointestinal Oncology &amp; Malignant Hematology, Moffitt Cancer Center &amp; Research Institute, Tampa, FL 33612, USA"},{"name":"Cancer Biology and Evolution Program, Moffitt Cancer Center &amp; Research Institute, Tampa, FL 33612, USA"},{"name":"Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7515-6515","authenticated-orcid":false,"given":"Michael B.","family":"Mann","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Moffitt Cancer Center &amp; Research Institute, Tampa, FL 33612, USA"},{"name":"Cancer Research Program, Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore"},{"name":"Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"},{"name":"Cancer Biology and Evolution Program, Moffitt Cancer Center &amp; Research Institute, Tampa, FL 33612, USA"},{"name":"Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA"},{"name":"Donald A. Adam Melanoma and Skin Cancer Research Center of Excellence, Moffitt Cancer Center, Tampa, FL 33612, USA"},{"name":"Department of Cutaneous Oncology, Moffitt Cancer Center &amp; Research Institute, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1126\/science.aau3879","article-title":"Somatic mutant clones colonize the human esophagus with age","volume":"362","author":"Martincorena","year":"2018","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1126\/science.aaa6806","article-title":"Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin","volume":"348","author":"Martincorena","year":"2015","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41586-018-0811-x","article-title":"Age-related remodelling of oesophageal epithelia by mutated cancer drivers","volume":"565","author":"Yokoyama","year":"2019","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/S0092-8674(00)80436-5","article-title":"Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells","volume":"91","author":"Ivics","year":"1997","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/gb-2007-8-s1-s15","article-title":"Transposons for cancer gene discovery: Sleeping Beauty and beyond","volume":"8","author":"Collier","year":"2007","journal-title":"Genome Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/nrc2916","article-title":"Harnessing transposons for cancer gene discovery","volume":"10","author":"Copeland","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature03691","article-title":"Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system","volume":"436","author":"Dupuy","year":"2005","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8150","DOI":"10.1158\/0008-5472.CAN-09-1135","article-title":"A modified Sleeping Beauty transposon system that can be used to model a wide variety of human cancers in mice","volume":"69","author":"Dupuy","year":"2009","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1038\/nbt.3637","article-title":"Analyzing tumor heterogeneity and driver genes in single myeloid leukemia cells with SBCapSeq","volume":"34","author":"Mann","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5934","DOI":"10.1073\/pnas.1202490109","article-title":"Sleeping Beauty mutagenesis reveals cooperating mutations and pathways in pancreatic adenocarcinoma","volume":"109","author":"Mann","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/ng.3275","article-title":"Transposon mutagenesis identifies genetic drivers of Braf (V600E) melanoma","volume":"47","author":"Mann","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_12","first-page":"235","article-title":"Transposon insertional mutagenesis models of cancer","volume":"3","author":"Mann","year":"2014","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"E7749","DOI":"10.1073\/pnas.1613859113","article-title":"Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression","volume":"113","author":"Rangel","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/ng.3175","article-title":"Transposon mutagenesis identifies genes and evolutionary forces driving gastrointestinal tract tumor progression","volume":"47","author":"Takeda","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.gde.2013.11.004","article-title":"Sleeping Beauty mutagenesis: Exploiting forward genetic screens for cancer gene discovery","volume":"24","author":"Mann","year":"2014","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mann, M.B., Aiderus, A., Newberg, J.Y., Guzman-Rojas, L., Contreras-Sandoval, A.M., Meshey, A.L., Jones, D.J., Amaya-Manzanares, F., Rangel, R., and Ward, J.M. (2020). Supplementary Tables 1\u201343 for Transposon mutagenesis identifies cooperating genetic drivers during keratinocyte transformation and cutaneous squamous cell carcinoma progression. Figshare, Available online: https:\/\/dx.doi.org\/10.35092\/yhjc.11441130.","DOI":"10.1371\/journal.pgen.1009094"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Aiderus, A., Newberg, J.Y., Guzman-Rojas, L., Contreras-Sandoval, A.M., Meshey, A.L., Jones, D.J., Amaya-Manzanares, F., Rangel, R., Ward, J.M., and Lee, S.-C. (2019). Transposon mutagenesis identifies cooperating genetic drivers during keratinocyte transformation and cutaneous squamous cell carcinoma progression. bioRxiv, Available online: https:\/\/dx.doi.org\/10.1101\/2019.12.24.887968.","DOI":"10.1101\/2019.12.24.887968"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e94","DOI":"10.1093\/nar\/gky450","article-title":"SB Driver Analysis: A Sleeping Beauty cancer driver analysis framework for identifying and prioritizing experimentally actionable oncogenes and tumor suppressors","volume":"46","author":"Newberg","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ymthe.2003.11.009","article-title":"Sleeping beauty transposition: Biology and applications for molecular therapy","volume":"9","author":"Izsvak","year":"2004","journal-title":"Mol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1006\/jmbi.2000.4047","article-title":"Sleeping Beauty, a wide host-range transposon vector for genetic transformation in vertebrates","volume":"302","author":"Izsvak","year":"2000","journal-title":"J. Mol. Biol."},{"key":"ref_21","unstructured":"Aiderus, A., Contreras-Sandoval, A.M., Meshey, A.L., Newberg, J., Ward, J.M., Swing, D., Copeland, N.G., Jenkins, N.A., Mann, K.M., and Mann, M.B. (2020, September 30). Table 1: SB Allele-Specific Tumor Spectrum by Whole-Body, Transposon-Mediated Mutagenesis in Wild Type Mice. Available online: https:\/\/dx.doi.org\/10.6084\/m9.figshare.12811685."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chen, E.Y., Tan, C.M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G.V., Clark, N.R., and Ma\u2019ayan, A. (2013). Enrichr: Interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-128"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: A comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1634\/theoncologist.2016-0030","article-title":"Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials","volume":"21","author":"Suh","year":"2016","journal-title":"Oncologist"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.trecan.2017.08.006","article-title":"KRAS Alleles: The Devil Is in the Detail","volume":"3","author":"Haigis","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nature13898","article-title":"The mutational landscapes of genetic and chemical models of Kras-driven lung cancer","volume":"517","author":"Westcott","year":"2015","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8258","DOI":"10.1038\/ncomms9258","article-title":"Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA","volume":"6","author":"Izumchenko","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s12032-014-0459-9","article-title":"RBMS3 is a tumor suppressor gene that acts as a favorable prognostic marker in lung squamous cell carcinoma","volume":"32","author":"Liang","year":"2015","journal-title":"Med. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"30091","DOI":"10.1074\/jbc.M501279200","article-title":"Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway","volume":"280","author":"Zhang","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"D1011","DOI":"10.1093\/nar\/gkx956","article-title":"SBCDDB: Sleeping Beauty Cancer Driver Database for gene discovery in mouse models of human cancers","volume":"46","author":"Newberg","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/ng.2847","article-title":"Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model","volume":"46","author":"Nguyen","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/hep.26004","article-title":"Sex bias occurrence of hepatocellular carcinoma in Poly7 molecular subclass is associated with EGFR","volume":"57","author":"Keng","year":"2013","journal-title":"Hepatology"},{"key":"ref_33","first-page":"E1377","article-title":"A Sleeping Beauty mutagenesis screen reveals a tumor suppressor role for Ncoa2\/Src-2 in liver cancer","volume":"109","author":"Keng","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.4049\/jimmunol.1203227","article-title":"Adaptive immunity does not strongly suppress spontaneous tumors in a Sleeping Beauty model of cancer","volume":"190","author":"Rogers","year":"2013","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Aiderus, A., Contreras-Sandoval, A.M., Meshey, A.L., Newberg, J.Y., Ward, J.M., Swing, D., Copeland, N.G., Jenkins, N.A., Mann, K.M., and Mann, M.B. (2020). SB-Onc2.3-Pan-TSG Trunk Driver SB insertion maps for \u201cPromoterless Transposon Mutagenesis Drives Solid Cancers via Tumor Suppressor Inactivation\u201d. Figshare.","DOI":"10.1101\/2020.08.17.254565"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41568-018-0060-1","article-title":"The COSMIC Cancer Gene Census: Describing genetic dysfunction across all human cancers","volume":"18","author":"Sondka","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/sj.bjc.6601894","article-title":"The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website","volume":"91","author":"Bamford","year":"2004","journal-title":"Br. J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"D652","DOI":"10.1093\/nar\/gkp995","article-title":"COSMIC (the Catalogue of Somatic Mutations in Cancer): A resource to investigate acquired mutations in human cancer","volume":"38","author":"Forbes","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"D1023","DOI":"10.1093\/nar\/gkv1268","article-title":"TSGene 2.0: An updated literature-based knowledgebase for tumor suppressor genes","volume":"44","author":"Zhao","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"D970","DOI":"10.1093\/nar\/gks937","article-title":"TSGene: A web resource for tumor suppressor genes","volume":"41","author":"Zhao","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/nature11114","article-title":"The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma","volume":"486","author":"Rust","year":"2012","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nature03681","article-title":"Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse","volume":"436","author":"Collier","year":"2005","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"E536","DOI":"10.1073\/pnas.1418163112","article-title":"BRAF inhibitor resistance mediated by the AKT pathway in an oncogenic BRAF mouse melanoma model","volume":"112","author":"Perna","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1126\/science.1163040","article-title":"A transposon-based genetic screen in mice identifies genes altered in colorectal cancer","volume":"323","author":"Starr","year":"2009","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/ng.3817","article-title":"A single-copy Sleeping Beauty transposon mutagenesis screen identifies new PTEN-cooperating tumor suppressor genes","volume":"49","author":"Weber","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1038\/s41467-019-09180-3","article-title":"PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice","volume":"10","author":"Weber","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"38968","DOI":"10.1038\/srep38968","article-title":"A CRISPR\/Cas9 Functional Screen Identifies Rare Tumor Suppressors","volume":"6","author":"Katigbak","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.cell.2008.09.061","article-title":"An oncogenomics-based in vivo RNAi screen identifies tumor suppressors in liver cancer","volume":"135","author":"Zender","year":"2008","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1038\/nprot.2009.120","article-title":"Multi-stage chemical carcinogenesis in mouse skin: Fundamentals and applications","volume":"4","author":"Abel","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"12601","DOI":"10.1038\/ncomms12601","article-title":"Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates","volume":"7","author":"Chitsazzadeh","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Hoshida, Y. (2019). Experimental Models for Preclinical Research in Hepatocellular Carcinoma. Hepatocellular Carcinoma: Translational Precision Medicine Approaches, Springer.","DOI":"10.1007\/978-3-030-21540-8"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.ccell.2018.02.003","article-title":"Loss of KDM6A Activates Super-Enhancers to Induce Gender-Specific Squamous-like Pancreatic Cancer and Confers Sensitivity to BET Inhibitors","volume":"33","author":"Andricovich","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6556","DOI":"10.1158\/1078-0432.CCR-17-1679","article-title":"KMT2C Mutations in Diffuse-Type Gastric Adenocarcinoma Promote Epithelial-to-Mesenchymal Transition","volume":"24","author":"Cho","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.molcel.2018.04.028","article-title":"MLL4 Is Required to Maintain Broad H3K4me3 Peaks and Super-Enhancers at Tumor Suppressor Genes","volume":"70","author":"Dhar","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1158\/2159-8290.CD-18-0385","article-title":"Crebbp Loss Drives Small Cell Lung Cancer and Increases Sensitivity to HDAC Inhibition","volume":"8","author":"Jia","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/ng.3744","article-title":"ARID1A loss impairs enhancer-mediated gene regulation and drives colon cancer in mice","volume":"49","author":"Mathur","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"E3978","DOI":"10.1073\/pnas.1716589115","article-title":"In vivo CRISPR screening unveils histone demethylase UTX as an important epigenetic regulator in lung tumorigenesis","volume":"115","author":"Wu","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1002\/path.5279","article-title":"CBP\/p300 antagonises EGFR-Ras-Erk signalling and suppresses increased Ras-Erk signalling-induced tumour formation in mice","volume":"249","author":"Ichise","year":"2019","journal-title":"J. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"17220","DOI":"10.1038\/s41598-019-53572-w","article-title":"Genome-wide CRISPR Screen to Identify Genes that Suppress Transformation in the Presence of Endogenous Kras(G12D)","volume":"9","author":"Huang","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5668","DOI":"10.1158\/0008-5472.CAN-18-0757","article-title":"Transcriptomics and Transposon Mutagenesis Identify Multiple Mechanisms of Resistance to the FGFR Inhibitor AZD4547","volume":"78","author":"Kas","year":"2018","journal-title":"Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1158\/1078-0432.CCR-17-2343","article-title":"RASA1 and NF1 are Preferentially Co-Mutated and Define A Distinct Genetic Subset of Smoking-Associated Non-Small Cell Lung Carcinomas Sensitive to MEK Inhibition","volume":"24","author":"Hayashi","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"E10417","DOI":"10.1073\/pnas.1808968115","article-title":"Molecular profiling of nonalcoholic fatty liver disease-associated hepatocellular carcinoma using SB transposon mutagenesis","volume":"115","author":"Kodama","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/nrc.2017.105","article-title":"Ubiquitin ligases in oncogenic transformation and cancer therapy","volume":"18","author":"Senft","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1158\/1541-7786.MCR-14-0674-T","article-title":"Transposon Mutagenesis Screen Identifies Potential Lung Cancer Drivers and CUL3 as a Tumor Suppressor","volume":"13","author":"Dorr","year":"2015","journal-title":"Mol. Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/s41598-020-57762-9","article-title":"The E3 ubiquitin ligase TRIP12 participates in cell cycle progression and chromosome stability","volume":"10","author":"Larrieu","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e12938","DOI":"10.1111\/acel.12938","article-title":"Decoy fitness peaks, tumor suppression, and aging","volume":"18","author":"Higa","year":"2019","journal-title":"Aging Cell"},{"key":"ref_67","unstructured":"Mann, M.B., and Mann, K.M. (2020). SB-Onc2.3 molecular cloning maps and files. Figshare, Available online: https:\/\/doi.org\/10.6084\/m9.figshare.12816452."},{"key":"ref_68","unstructured":"Mann, M.B., and Mann, K.M. (2020). SB-Onc2.3 multiplex PCR genotyping protocol. Figshare, Available online: https:\/\/doi.org\/10.6084\/m9.figshare.12811301."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1101\/SQB.1997.062.01.021","article-title":"Analysis of Fgf8 gene function in vertebrate development","volume":"62","author":"Lewandoski","year":"1997","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/ng747","article-title":"Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer","volume":"29","author":"Jonkers","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.cell.2004.11.004","article-title":"Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome","volume":"119","author":"Olive","year":"2004","journal-title":"Cell"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Aiderus, A., Contreras-Sandoval, A.M., Meshey, A.L., Newberg, J.Y., Ward, J.M., Swing, D., Copeland, N.G., Jenkins, N.A., Mann, K.M., and Mann, M.B. (2020). Onc2.3 pathology images for \u201cPromoterless Transposon Mutagenesis Drives Solid Cancers via Tumor Suppressor Inactivation\u201d. Figshare, Available online: https:\/\/dx.doi.org\/10.6084\/m9.figshare.12816305.","DOI":"10.1101\/2020.08.17.254565"},{"key":"ref_73","unstructured":"Mann, M.B., Mann, K.M., Contreras-Sandoval, A.M., Guzman-Rojas, L., Newberg, J.Y., Meshey, A.L., Jones, D.J., Amaya-Manzanares, F., Copeland, N.G., and Jenkins, N.A. (2019). SBCapSeq Protocol manuscript files for \u201cQuantifying tumor heterogeneity, clonal dynamics, and cancer driver gene evolution from Sleeping Beauty transposon mutagenesis models using SBCapSeq\u201d. Natl. Inst. Health Dataset, Available online: https:\/\/dx.doi.org\/10.35092\/yhjc.11441001."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Mann, K.M., Mann, M.B., Guzman-Rojas, L., Amaya-Manzanares, F., Jones, D.J., Newberg, J.Y., Jenkins, N.A., and Copeland, N.G. (2016). SBCapSeq Protocol: A method for selective cloning of Sleeping Beauty transposon insertions using liquid capture hybridization and Ion Torrent semiconductor sequencing. Protoc. Exch.","DOI":"10.1038\/protex.2016.053"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/ng.990","article-title":"Insertional mutagenesis identifies multiple networks of cooperating genes driving intestinal tumorigenesis","volume":"43","author":"March","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_76","unstructured":"Mann, M.B., and Mann, K.M. (2020). SB-Onc2.3 donor chromosome dataset. Figshare, Available online: https:\/\/dx.doi.org\/10.6084\/m9.figshare.12816191."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Aiderus, A., Contreras-Sandoval, A.M., Meshey, A.L., Newberg, J.Y., Ward, J.M., Swing, D., Copeland, N.G., Jenkins, N.A., Mann, K.M., and Mann, M.B. (2020). Supplementary Notes 1\u20133 for \u201cPromoterless Transposon Mutagenesis Drives Solid Cancers via Tumor Suppressor Inactivation\u201d. Figshare, Available online: https:\/\/dx.doi.org\/10.6084\/m9.figshare.12811979.","DOI":"10.1101\/2020.08.17.254565"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Aiderus, A., Contreras-Sandoval, A.M., Meshey, A.L., Newberg, J.Y., Ward, J.M., Swing, D., Copeland, N.G., Jenkins, N.A., Mann, K.M., and Mann, M.B. (2020). Supplementary Tables 1\u201324 for \u201cPromoterless Transposon Mutagenesis Drives Solid Cancers via Tumor Suppressor Inactivation\u201d. 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