{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:10:18Z","timestamp":1787987418944,"version":"build-2784847793"},"update-to":[{"DOI":"10.1371\/journal.pgen.1009986","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000}}],"reference-count":153,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000983","name":"Mary Kay Foundation","doi-asserted-by":"publisher","award":["026-16"],"award-info":[{"award-number":["026-16"]}],"id":[{"id":"10.13039\/100000983","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["PF-17-163-02-DDC"],"award-info":[{"award-number":["PF-17-163-02-DDC"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>TP53 and ARID1A are frequently mutated across cancer but rarely in the same primary tumor. Endometrial cancer has the highest TP53-ARID1A mutual exclusivity rate. However, the functional relationship between TP53 and ARID1A mutations in the endometrium has not been elucidated. We used genetically engineered mice and <jats:italic>in vivo<\/jats:italic> genomic approaches to discern both unique and overlapping roles of TP53 and ARID1A in the endometrium. TP53 loss with oncogenic PIK3CA<jats:sup>H1047R<\/jats:sup> in the endometrial epithelium results in features of endometrial hyperplasia, adenocarcinoma, and intraepithelial carcinoma. Mutant endometrial epithelial cells were transcriptome profiled and compared to control cells and ARID1A\/PIK3CA mutant endometrium. In the context of either TP53 or ARID1A loss, PIK3CA mutant endometrium exhibited inflammatory pathway activation, but other gene expression programs differed based on TP53 or ARID1A status, such as epithelial-to-mesenchymal transition. Gene expression patterns observed in the genetic mouse models are reflective of human tumors with each respective genetic alteration. Consistent with TP53-ARID1A mutual exclusivity, the p53 pathway is activated following ARID1A loss in the endometrial epithelium, where ARID1A normally directly represses p53 pathway genes <jats:italic>in vivo<\/jats:italic>, including the stress-inducible transcription factor, ATF3. However, co-existing TP53-ARID1A mutations led to invasive adenocarcinoma associated with mutant ARID1A-driven ATF3 induction, reduced apoptosis, TP63+ squamous differentiation and invasion. These data suggest TP53 and ARID1A mutations drive shared and distinct tumorigenic programs in the endometrium and promote invasive endometrial cancer when existing simultaneously. Hence, TP53 and ARID1A mutations may co-occur in a subset of aggressive or metastatic endometrial cancers, with ARID1A loss promoting squamous differentiation and the acquisition of invasive properties.<\/jats:p>","DOI":"10.1371\/journal.pgen.1009986","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T18:53:13Z","timestamp":1640285593000},"page":"e1009986","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":42,"title":["Co-existing TP53 and ARID1A mutations promote aggressive endometrial tumorigenesis"],"prefix":"10.1371","volume":"17","author":[{"given":"Jake J.","family":"Reske","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7681-2457","authenticated-orcid":true,"given":"Mike R.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6081-7413","authenticated-orcid":true,"given":"Jeanne","family":"Holladay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-3782","authenticated-orcid":true,"given":"Rebecca A.","family":"Siwicki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9774-4844","authenticated-orcid":true,"given":"Hilary","family":"Skalski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7272-9197","authenticated-orcid":true,"given":"Shannon","family":"Harkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7909-2339","authenticated-orcid":true,"given":"Marie","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1280-1326","authenticated-orcid":true,"given":"John I.","family":"Risinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galen","family":"Hostetter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8516-7971","authenticated-orcid":true,"given":"Ken","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5775-2594","authenticated-orcid":true,"given":"Ronald L.","family":"Chandler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"issue":"7484","key":"pgen.1009986.ref001","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nature12912","article-title":"Discovery and saturation analysis of cancer genes across 21 tumour types","volume":"505","author":"MS Lawrence","year":"2014","journal-title":"Nature"},{"issue":"5701","key":"pgen.1009986.ref002","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/278261a0","article-title":"T antigen is bound to a host protein in SV40-transformed cells","volume":"278","author":"DP Lane","year":"1979","journal-title":"Nature"},{"issue":"6","key":"pgen.1009986.ref003","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.cell.2017.08.028","article-title":"Putting p53 in Context.","volume":"170","author":"ER Kastenhuber","year":"2017","journal-title":"Cell"},{"issue":"1","key":"pgen.1009986.ref004","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1158\/2159-8290.CD-12-0361","article-title":"ARID1A mutations in cancer: another epigenetic tumor suppressor?","volume":"3","author":"JN Wu","year":"2013","journal-title":"Cancer Discov."},{"issue":"5","key":"pgen.1009986.ref005","doi-asserted-by":"crossref","first-page":"e1500447","DOI":"10.1126\/sciadv.1500447","article-title":"Mammalian SWI\/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics","volume":"1","author":"C Kadoch","year":"2015","journal-title":"Sci Adv"},{"issue":"1","key":"pgen.1009986.ref006","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/cdd.2017.174","article-title":"Mechanisms of transcriptional regulation by p53","volume":"25","author":"KD Sullivan","year":"2018","journal-title":"Cell Death Differ"},{"issue":"20","key":"pgen.1009986.ref007","doi-asserted-by":"crossref","first-page":"9236","DOI":"10.1158\/0008-5472.CAN-05-1225","article-title":"The p270 (ARID1A\/SMARCF1) subunit of mammalian SWI\/SNF-related complexes is essential for normal cell cycle arrest.","volume":"65","author":"NG Nagl","year":"2005","journal-title":"Cancer Res"},{"issue":"7","key":"pgen.1009986.ref008","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1158\/2159-8290.CD-14-0849","article-title":"ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors.","volume":"5","author":"J Shen","year":"2015","journal-title":"Cancer Discov"},{"issue":"5","key":"pgen.1009986.ref009","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a026070","article-title":"p53 in the DNA-Damage-Repair Process.","volume":"6","author":"AB Williams","year":"2016","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"7","key":"pgen.1009986.ref010","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/S0344-0338(96)80088-4","article-title":"The role of p53 in cell cycle regulation","volume":"192","author":"PH Shaw","year":"1996","journal-title":"Pathol Res Pract"},{"issue":"1 Pt 1","key":"pgen.1009986.ref011","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/S0002-9378(94)70414-7","article-title":"The p53 tumor suppressor gene frequently is altered in gynecologic cancers","volume":"170","author":"A Berchuck","year":"1994","journal-title":"Am J Obstet Gynecol"},{"issue":"4","key":"pgen.1009986.ref012","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.ccell.2018.03.014","article-title":"A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers","volume":"33","author":"AC Berger","year":"2018","journal-title":"Cancer Cell"},{"issue":"16","key":"pgen.1009986.ref013","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa1008433","article-title":"ARID1A mutations in endometriosis-associated ovarian carcinomas","volume":"363","author":"KC Wiegand","year":"2010","journal-title":"N Engl J Med"},{"issue":"6001","key":"pgen.1009986.ref014","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1126\/science.1196333","article-title":"Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma","volume":"330","author":"S Jones","year":"2010","journal-title":"Science"},{"issue":"12","key":"pgen.1009986.ref015","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1038\/ng.2455","article-title":"Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes.","volume":"44","author":"Le Gallo M","year":"2012","journal-title":"Nat Genet"},{"issue":"17","key":"pgen.1009986.ref016","doi-asserted-by":"crossref","first-page":"3261","DOI":"10.1002\/cncr.30745","article-title":"Somatic mutation profiles of clear cell endometrial tumors revealed by whole exome and targeted gene sequencing","volume":"123","author":"M Le Gallo","year":"2017","journal-title":"Cancer"},{"issue":"3","key":"pgen.1009986.ref017","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S0090-8258(02)00149-X","article-title":"p53 mutations and overexpression affect prognosis of ovarian endometrioid cancer but not clear cell cancer","volume":"88","author":"T Okuda","year":"2003","journal-title":"Gynecol Oncol"},{"issue":"7447","key":"pgen.1009986.ref018","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nature12113","article-title":"Integrated genomic characterization of endometrial carcinoma","volume":"497","author":"Cancer Genome Atlas Research N","year":"2013","journal-title":"Nature"},{"issue":"1","key":"pgen.1009986.ref019","first-page":"177","article-title":"p53 gene mutations are common in uterine serous carcinoma and occur early in their pathogenesis","volume":"150","author":"H Tashiro","year":"1997","journal-title":"Am J Pathol"},{"issue":"3","key":"pgen.1009986.ref020","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.ccell.2017.02.010","article-title":"Integrated Molecular Characterization of Uterine Carcinosarcoma","volume":"31","author":"AD Cherniack","year":"2017","journal-title":"Cancer Cell"},{"issue":"7353","key":"pgen.1009986.ref021","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/nature10166","article-title":"Integrated genomic analyses of ovarian carcinoma.","volume":"474","author":"Cancer Genome Atlas Research N","year":"2011","journal-title":"Nature"},{"issue":"21","key":"pgen.1009986.ref022","doi-asserted-by":"crossref","first-page":"6718","DOI":"10.1158\/0008-5472.CAN-11-1562","article-title":"ARID1A, a factor that promotes formation of SWI\/SNF-mediated chromatin remodeling, is a tumor suppressor in gynecologic cancers","volume":"71","author":"B Guan","year":"2011","journal-title":"Cancer Res"},{"issue":"3","key":"pgen.1009986.ref023","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/onc.2012.586","article-title":"Next-generation sequencing of endoscopic biopsies identifies ARID1A as a tumor-suppressor gene in Barrett\u2019s esophagus","volume":"33","author":"MM Streppel","year":"2014","journal-title":"Oncogene"},{"issue":"4","key":"pgen.1009986.ref024","doi-asserted-by":"crossref","first-page":"339","DOI":"10.4048\/jbc.2015.18.4.339","article-title":"Loss of Tumor Suppressor ARID1A Protein Expression Correlates with Poor Prognosis in Patients with Primary Breast Cancer","volume":"18","author":"HD Cho","year":"2015","journal-title":"J Breast Cancer"},{"issue":"12","key":"pgen.1009986.ref025","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1038\/ng.982","article-title":"Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer","volume":"43","author":"K Wang","year":"2011","journal-title":"Nat Genet"},{"issue":"5","key":"pgen.1009986.ref026","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/ng.2246","article-title":"Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes","volume":"44","author":"ZJ Zang","year":"2012","journal-title":"Nat Genet"},{"issue":"2","key":"pgen.1009986.ref027","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/modpathol.2013.144","article-title":"ARID1A loss correlates with mismatch repair deficiency and intact p53 expression in high-grade endometrial carcinomas.","volume":"27","author":"G Allo","year":"2014","journal-title":"Mod Pathol."},{"issue":"11","key":"pgen.1009986.ref028","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1038\/modpathol.2013.96","article-title":"Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations, TP53 and microsatellite instability in endometrial cancer","volume":"26","author":"T Bosse","year":"2013","journal-title":"Mod Pathol"},{"issue":"3","key":"pgen.1009986.ref029","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cels.2018.03.002","article-title":"Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines.","volume":"6","author":"K Ellrott","year":"2018","journal-title":"Cell Syst"},{"issue":"2","key":"pgen.1009986.ref030","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.cell.2018.03.022","article-title":"Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer","volume":"173","author":"KA Hoadley","year":"2018","journal-title":"Cell"},{"issue":"10023","key":"pgen.1009986.ref031","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/S0140-6736(15)00130-0","article-title":"Endometrial cancer.","volume":"387","author":"P Morice","year":"2016","journal-title":"Lancet"},{"issue":"9","key":"pgen.1009986.ref032","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/s41568-019-0177-x","article-title":"Clinical actionability of molecular targets in endometrial cancer","volume":"19","author":"ME Urick","year":"2019","journal-title":"Nat Rev Cancer"},{"issue":"7447","key":"pgen.1009986.ref033","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nature12113","article-title":"Integrated genomic characterization of endometrial carcinoma","volume":"497","author":"Cancer Genome Atlas Research Network","year":"2013","journal-title":"Nature"},{"issue":"1","key":"pgen.1009986.ref034","doi-asserted-by":"crossref","first-page":"3554","DOI":"10.1038\/s41467-019-11403-6","article-title":"ARID1A and PI3-kinase pathway mutations in the endometrium drive epithelial transdifferentiation and collective invasion.","volume":"10","author":"MR Wilson","year":"2019","journal-title":"Nat Commun."},{"issue":"1","key":"pgen.1009986.ref035","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1093\/humrep\/dez253","article-title":"A mouse model of endometriosis mimicking the natural spread of invasive endometrium","volume":"35","author":"MR Wilson","year":"2020","journal-title":"Hum Reprod"},{"issue":"8","key":"pgen.1009986.ref036","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1101\/gad.14.8.994","article-title":"Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum","volume":"14","author":"S Marino","year":"2000","journal-title":"Genes Dev"},{"issue":"7","key":"pgen.1009986.ref037","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1158\/0008-5472.CAN-10-0738","article-title":"Cooperation between Pik3ca and p53 mutations in mouse mammary tumor formation","volume":"71","author":"JR Adams","year":"2011","journal-title":"Cancer Res"},{"issue":"7","key":"pgen.1009986.ref038","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1210\/en.2014-1265","article-title":"Lactoferrin-iCre: a new mouse line to study uterine epithelial gene function","volume":"155","author":"T Daikoku","year":"2014","journal-title":"Endocrinology"},{"issue":"3","key":"pgen.1009986.ref039","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0090-8258(82)90076-2","article-title":"Adenocarcinoma of the endometrium: analysis of 256 cases with carcinoma limited to the uterine corpus. Pathology review and analysis of prognostic variables","volume":"13","author":"M Hendrickson","year":"1982","journal-title":"Gynecol Oncol"},{"issue":"7","key":"pgen.1009986.ref040","doi-asserted-by":"crossref","first-page":"e268","DOI":"10.1016\/S1470-2045(13)70591-6","article-title":"Classification of endometrial carcinoma: more than two types","volume":"15","author":"R Murali","year":"2014","journal-title":"Lancet Oncol"},{"issue":"5","key":"pgen.1009986.ref041","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1097\/00000478-200005000-00012","article-title":"Endometrial intraepithelial carcinoma with associated peritoneal carcinomatosis.","volume":"24","author":"RA Soslow","year":"2000","journal-title":"Am J Surg Pathol"},{"key":"pgen.1009986.ref042","doi-asserted-by":"crossref","first-page":"117","DOI":"10.2147\/CMAR.S45141","article-title":"Serous endometrial intraepithelial carcinoma: a case series and literature review","volume":"5","author":"P Pathiraja","year":"2013","journal-title":"Cancer Manag Res"},{"issue":"11","key":"pgen.1009986.ref043","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1016\/0046-8177(95)90203-1","article-title":"Endometrial intraepithelial carcinoma: a distinctive lesion specifically associated with tumors displaying serous differentiation","volume":"26","author":"RA Ambros","year":"1995","journal-title":"Hum Pathol"},{"issue":"43","key":"pgen.1009986.ref044","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"A Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"pgen.1009986.ref045","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection.","volume":"1","author":"A Liberzon","year":"2015","journal-title":"Cell Syst"},{"issue":"23","key":"pgen.1009986.ref046","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.235127","article-title":"Molecular regulation of Snai2 in development and disease","volume":"132","author":"W Zhou","year":"2019","journal-title":"J Cell Sci"},{"issue":"10","key":"pgen.1009986.ref047","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1101\/gr.220533.117","article-title":"Identification of a core TP53 transcriptional program with highly distributed tumor suppressive activity","volume":"27","author":"Z Andrysik","year":"2017","journal-title":"Genome Res"},{"issue":"3","key":"pgen.1009986.ref048","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.cell.2008.12.002","article-title":"PH domain-only protein PHLDA3 is a p53-regulated repressor of Akt","volume":"136","author":"T Kawase","year":"2009","journal-title":"Cell"},{"issue":"12","key":"pgen.1009986.ref049","doi-asserted-by":"crossref","first-page":"i237","DOI":"10.1093\/bioinformatics\/btq182","article-title":"Inference of patient-specific pathway activities from multi-dimensional cancer genomics data using PARADIGM","volume":"26","author":"CJ Vaske","year":"2010","journal-title":"Bioinformatics"},{"issue":"6","key":"pgen.1009986.ref050","doi-asserted-by":"crossref","first-page":"108366","DOI":"10.1016\/j.celrep.2020.108366","article-title":"ARID1A Mutations Promote P300-Dependent Endometrial Invasion through Super-Enhancer Hyperacetylation","volume":"33","author":"MR Wilson","year":"2020","journal-title":"Cell Rep"},{"key":"pgen.1009986.ref051","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.21856","article-title":"An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites","volume":"6","author":"PJ Skene","year":"2017","journal-title":"Elife"},{"issue":"6","key":"pgen.1009986.ref052","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nm.4333","article-title":"Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients","volume":"23","author":"A Zehir","year":"2017","journal-title":"Nat Med"},{"key":"pgen.1009986.ref053","article-title":"Extracting Biological Insights from the Project Achilles Genome-Scale CRISPR Screens in Cancer Cell Lines.","author":"JM Dempster","year":"2019","journal-title":"bioRxiv"},{"issue":"5","key":"pgen.1009986.ref054","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.ccell.2017.10.007","article-title":"Arid1a Has Context-Dependent Oncogenic and Tumor Suppressor Functions in Liver Cancer","volume":"32","author":"X Sun","year":"2017","journal-title":"Cancer Cell"},{"issue":"3","key":"pgen.1009986.ref055","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s12253-017-0338-8","article-title":"Low Arid1a Expression Correlates with Poor Prognosis and Promotes Cell Proliferation and Metastasis in Osteosarcoma.","volume":"25","author":"N Xu","year":"2019","journal-title":"Pathol Oncol Res"},{"key":"pgen.1009986.ref056","doi-asserted-by":"crossref","first-page":"e10464","DOI":"10.7717\/peerj.10464","article-title":"ARID1A alterations and their clinical significance in cholangiocarcinoma.","volume":"8","author":"A Namjan","year":"2020","journal-title":"PeerJ"},{"issue":"2","key":"pgen.1009986.ref057","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ccell.2017.07.005","article-title":"Genomic Evolution of Breast Cancer Metastasis and Relapse","volume":"32","author":"LR Yates","year":"2017","journal-title":"Cancer Cell"},{"issue":"48","key":"pgen.1009986.ref058","doi-asserted-by":"crossref","first-page":"18404","DOI":"10.3748\/wjg.v20.i48.18404","article-title":"Clinicopathologic and prognostic relevance of ARID1A protein loss in colorectal cancer","volume":"20","author":"XL Wei","year":"2014","journal-title":"World J Gastroenterol"},{"issue":"8","key":"pgen.1009986.ref059","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/ng.3602","article-title":"The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis","volume":"48","author":"WJ Gibson","year":"2016","journal-title":"Nat Genet"},{"issue":"4\u20136","key":"pgen.1009986.ref060","first-page":"321","article-title":"ATF3 and stress responses","volume":"7","author":"T Hai","year":"1999","journal-title":"Gene Expr"},{"issue":"15","key":"pgen.1009986.ref061","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1038\/sj.onc.1210861","article-title":"A potential dichotomous role of ATF3, an adaptive-response gene, in cancer development","volume":"27","author":"X Yin","year":"2008","journal-title":"Oncogene"},{"issue":"7296","key":"pgen.1009986.ref062","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nature08996","article-title":"Opposing roles for calcineurin and ATF3 in squamous skin cancer","volume":"465","author":"X Wu","year":"2010","journal-title":"Nature"},{"issue":"3","key":"pgen.1009986.ref063","doi-asserted-by":"crossref","first-page":"e13315","DOI":"10.1111\/acel.13315","article-title":"ATF3 drives senescence by reconstructing accessible chromatin profiles","volume":"20","author":"C Zhang","year":"2021","journal-title":"Aging Cell"},{"issue":"6","key":"pgen.1009986.ref064","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1002\/1878-0261.12172","article-title":"p53-independent Noxa induction by cisplatin is regulated by ATF3\/ATF4 in head and neck squamous cell carcinoma cells","volume":"12","author":"K Sharma","year":"2018","journal-title":"Mol Oncol"},{"issue":"13","key":"pgen.1009986.ref065","doi-asserted-by":"crossref","first-page":"5721","DOI":"10.1128\/MCB.24.13.5721-5732.2004","article-title":"Role for activating transcription factor 3 in stress-induced beta-cell apoptosis","volume":"24","author":"MG Hartman","year":"2004","journal-title":"Mol Cell Biol"},{"issue":"10","key":"pgen.1009986.ref066","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12102918","article-title":"Time-Resolved Profiling Reveals ATF3 as a Novel Mediator of Endocrine Resistance in Breast Cancer.","volume":"12","author":"S Borgoni","year":"2020","journal-title":"Cancers (Basel)."},{"issue":"18","key":"pgen.1009986.ref067","doi-asserted-by":"crossref","first-page":"8569","DOI":"10.18632\/oncotarget.2322","article-title":"ATF3 functions as a novel tumor suppressor with prognostic significance in esophageal squamous cell carcinoma","volume":"5","author":"JJ Xie","year":"2014","journal-title":"Oncotarget"},{"key":"pgen.1009986.ref068","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1186\/1471-2407-8-268","article-title":"The transcription factor ATF3 acts as an oncogene in mouse mammary tumorigenesis","volume":"8","author":"A Wang","year":"2008","journal-title":"BMC Cancer"},{"issue":"17","key":"pgen.1009986.ref069","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1038\/s41388-021-01771-z","article-title":"Loss of activating transcription factor 3 prevents KRAS-mediated pancreatic cancer","volume":"40","author":"N Azizi","year":"2021","journal-title":"Oncogene"},{"issue":"17","key":"pgen.1009986.ref070","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1038\/onc.2011.397","article-title":"Key role of ATF3 in p53-dependent DR5 induction upon DNA damage of human colon cancer cells","volume":"31","author":"K Taketani","year":"2012","journal-title":"Oncogene"},{"issue":"15","key":"pgen.1009986.ref071","doi-asserted-by":"crossref","first-page":"10473","DOI":"10.1074\/jbc.M509278200","article-title":"Activating transcription factor 3, a stress-inducible gene, suppresses Ras-stimulated tumorigenesis","volume":"281","author":"D Lu","year":"2006","journal-title":"J Biol Chem"},{"issue":"10","key":"pgen.1009986.ref072","doi-asserted-by":"crossref","first-page":"e26848","DOI":"10.1371\/journal.pone.0026848","article-title":"Systems analysis of ATF3 in stress response and cancer reveals opposing effects on pro-apoptotic genes in p53 pathway.","volume":"6","author":"Y Tanaka","year":"2011","journal-title":"PLoS One."},{"key":"pgen.1009986.ref073","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1186\/s12864-016-2664-8","article-title":"The common stress responsive transcription factor ATF3 binds genomic sites enriched with p300 and H3K27ac for transcriptional regulation","volume":"17","author":"J Zhao","year":"2016","journal-title":"BMC Genomics"},{"issue":"6","key":"pgen.1009986.ref074","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1038\/s41418-019-0463-x","article-title":"Competitive ubiquitination activates the tumor suppressor p53","volume":"27","author":"X Li","year":"2020","journal-title":"Cell Death Differ"},{"issue":"9","key":"pgen.1009986.ref075","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1073\/pnas.88.9.3720","article-title":"Cross-family dimerization of transcription factors Fos\/Jun and ATF\/CREB alters DNA binding specificity","volume":"88","author":"T Hai","year":"1991","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"pgen.1009986.ref076","doi-asserted-by":"crossref","first-page":"e1009283","DOI":"10.1371\/journal.pgen.1009283","article-title":"ATF3 downmodulates its new targets IFI6 and IFI27 to suppress the growth and migration of tongue squamous cell carcinoma cells","volume":"17","author":"L Xu","year":"2021","journal-title":"PLoS Genet"},{"key":"pgen.1009986.ref077","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s11658-018-0094-0","article-title":"MicroRNA-488 inhibits tongue squamous carcinoma cell invasion and EMT by directly targeting ATF3","volume":"23","author":"B Shi","year":"2018","journal-title":"Cell Mol Biol Lett"},{"issue":"6","key":"pgen.1009986.ref078","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/mc.20298","article-title":"Epidermal hyperplasia and oral carcinoma in mice overexpressing the transcription factor ATF3 in basal epithelial cells","volume":"46","author":"A Wang","year":"2007","journal-title":"Mol Carcinog"},{"key":"pgen.1009986.ref079","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.63266","article-title":"Dissecting the DNA binding landscape and gene regulatory network of p63 and p53.","volume":"9","author":"K Riege","year":"2020","journal-title":"Elife"},{"issue":"3","key":"pgen.1009986.ref080","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1097\/00004347-200107000-00002","article-title":"Early uterine serous carcinoma: clonal origin of extrauterine disease.","volume":"20","author":"RN Baergen","year":"2001","journal-title":"Int J Gynecol Pathol"},{"issue":"51","key":"pgen.1009986.ref081","doi-asserted-by":"crossref","first-page":"25880","DOI":"10.1073\/pnas.1911310116","article-title":"Fbxw7 is a driver of uterine carcinosarcoma by promoting epithelial-mesenchymal transition","volume":"116","author":"IC Cuevas","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"pgen.1009986.ref082","first-page":"2207","article-title":"Synchronous endometrioid endometrial and ovarian carcinomas are biologically related: A clinico-pathological and molecular (next generation sequencing) study of 22 cases.","volume":"17","author":"N Hajkova","year":"2019","journal-title":"Oncol Lett."},{"issue":"4","key":"pgen.1009986.ref083","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1093\/carcin\/bgt398","article-title":"Reduced expression of the chromatin remodeling gene ARID1A enhances gastric cancer cell migration and invasion via downregulation of E-cadherin transcription","volume":"35","author":"HB Yan","year":"2014","journal-title":"Carcinogenesis"},{"key":"pgen.1009986.ref084","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13046-015-0164-3","article-title":"Decreased expression of ARID1A associates with poor prognosis and promotes metastases of hepatocellular carcinoma","volume":"34","author":"F He","year":"2015","journal-title":"J Exp Clin Cancer Res"},{"key":"pgen.1009986.ref085","doi-asserted-by":"crossref","DOI":"10.1177\/1533034618754475","article-title":"Loss of ARID1A Expression Correlates With Tumor Differentiation and Tumor Progression Stage in Pancreatic Ductal Adenocarcinoma.","volume":"17","author":"L Zhang","year":"2018","journal-title":"Technol Cancer Res Treat"},{"key":"pgen.1009986.ref086","doi-asserted-by":"crossref","first-page":"4931","DOI":"10.2147\/CMAR.S207329","article-title":"Loss of ARID1A promotes proliferation, migration and invasion via the Akt signaling pathway","volume":"11","author":"Y Yang","year":"2019","journal-title":"NPC. Cancer Manag Res"},{"issue":"16","key":"pgen.1009986.ref087","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1016\/j.febslet.2014.02.011","article-title":"p53: the barrier to cancer stem cell formation","volume":"588","author":"R Aloni-Grinstein","year":"2014","journal-title":"FEBS Lett"},{"issue":"4","key":"pgen.1009986.ref088","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1158\/2159-8290.CD-13-0136","article-title":"Contribution of p53 to metastasis","volume":"4","author":"E Powell","year":"2014","journal-title":"Cancer Discov"},{"issue":"14","key":"pgen.1009986.ref089","doi-asserted-by":"crossref","first-page":"5619","DOI":"10.1158\/0008-5472.CAN-08-1274","article-title":"Conditional loss of uterine Pten unfailingly and rapidly induces endometrial cancer in mice","volume":"68","author":"T Daikoku","year":"2008","journal-title":"Cancer Res"},{"issue":"8","key":"pgen.1009986.ref090","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1002\/emmm.201101063","article-title":"p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans","volume":"4","author":"PJ Wild","year":"2012","journal-title":"EMBO Mol Med"},{"issue":"17","key":"pgen.1009986.ref091","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1038\/onc.2012.232","article-title":"Cooperation between p53 and the telomere-protecting shelterin component Pot1a in endometrial carcinogenesis","volume":"32","author":"EA Akbay","year":"2013","journal-title":"Oncogene"},{"issue":"10","key":"pgen.1009986.ref092","first-page":"2170","article-title":"Reversal of obesity-driven aggressiveness of endometrial cancer by metformin","volume":"9","author":"H Guo","year":"2019","journal-title":"Am J Cancer Res"},{"key":"pgen.1009986.ref093","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev-pathol-121808-102144","article-title":"The senescence-associated secretory phenotype: the dark side of tumor suppression.","volume":"5","author":"JP Coppe","year":"2010","journal-title":"Annu Rev Pathol"},{"issue":"4","key":"pgen.1009986.ref094","doi-asserted-by":"crossref","first-page":"a001115","DOI":"10.1101\/cshperspect.a001115","article-title":"Mouse models of p53 functions.","volume":"2","author":"G. Lozano","year":"2010","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"4","key":"pgen.1009986.ref095","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/PGP.0000000000000243","article-title":"TP53 Mutational Spectrum in Endometrioid and Serous Endometrial Cancers.","volume":"35","author":"AM Schultheis","year":"2016","journal-title":"Int J Gynecol Pathol."},{"issue":"4","key":"pgen.1009986.ref096","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12040905","article-title":"ARID1A Regulates Transcription and the Epigenetic Landscape via POLE and DMAP1 while ARID1A Deficiency or Pharmacological Inhibition Sensitizes Germ Cell Tumor Cells to ATR Inhibition.","volume":"12","author":"L Kurz","year":"2020","journal-title":"Cancers (Basel)."},{"issue":"6","key":"pgen.1009986.ref097","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1309\/21TW-2NDG-JRK4-PFJX","article-title":"Value of p63 and cytokeratin 5\/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas","volume":"116","author":"O Kaufmann","year":"2001","journal-title":"Am J Clin Pathol"},{"issue":"3","key":"pgen.1009986.ref098","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1097\/PGP.0b013e31826129e1","article-title":"Immunohistochemical characterization of squamous differentiation and morular metaplasia in uterine endometrioid adenocarcinoma","volume":"32","author":"LZ Blanco","year":"2013","journal-title":"Int J Gynecol Pathol"},{"issue":"2","key":"pgen.1009986.ref099","first-page":"154","article-title":"Squamous differentiation in carcinoma of the endometrium: a critical appraisal of adenoacanthoma and adenosquamous carcinoma","volume":"5","author":"RJ Zaino","year":"1988","journal-title":"Semin Diagn Pathol"},{"issue":"10","key":"pgen.1009986.ref100","doi-asserted-by":"crossref","first-page":"e0220086","DOI":"10.1371\/journal.pone.0220086","article-title":"Squamous differentiation portends poor prognosis in low and intermediate-risk endometrioid endometrial cancer","volume":"14","author":"DAP Andrade","year":"2019","journal-title":"PLoS One"},{"issue":"12","key":"pgen.1009986.ref101","doi-asserted-by":"crossref","first-page":"14885","DOI":"10.18632\/oncotarget.7450","article-title":"Glucose-regulated protein 94 deficiency induces squamous cell metaplasia and suppresses PTEN-null driven endometrial epithelial tumor development","volume":"7","author":"J Shen","year":"2016","journal-title":"Oncotarget"},{"issue":"6","key":"pgen.1009986.ref102","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1038\/s41418-019-0475-6","article-title":"ARID1A prevents squamous cell carcinoma initiation and chemoresistance by antagonizing pRb\/E2F1\/c-Myc-mediated cancer stemness","volume":"27","author":"Q Luo","year":"2020","journal-title":"Cell Death Differ"},{"issue":"11","key":"pgen.1009986.ref103","doi-asserted-by":"crossref","DOI":"10.3390\/genes11111368","article-title":"SWI\/SNF Alterations in Squamous Bladder Cancers.","volume":"11","author":"F Achenbach","year":"2020","journal-title":"Genes (Basel)."},{"issue":"7","key":"pgen.1009986.ref104","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.ajpath.2021.03.013","article-title":"Vaginal Squamous Cell Carcinoma Develops in Mice with Conditional Arid1a Loss and Gain of Oncogenic Kras Driven by Progesterone Receptor Cre","volume":"191","author":"X Wang","year":"2021","journal-title":"Am J Pathol"},{"issue":"1","key":"pgen.1009986.ref105","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/onc.2008.363","article-title":"beta-catenin mediates glandular formation and dysregulation of beta-catenin induces hyperplasia formation in the murine uterus","volume":"28","author":"JW Jeong","year":"2009","journal-title":"Oncogene"},{"issue":"1","key":"pgen.1009986.ref106","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1006\/gyno.2000.6026","article-title":"Identification of a basal\/reserve cell immunophenotype in benign and neoplastic endometrium: a study with the p53 homologue p63","volume":"80","author":"JT O\u2019Connell","year":"2001","journal-title":"Gynecol Oncol"},{"issue":"5","key":"pgen.1009986.ref107","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1016\/j.celrep.2016.09.093","article-title":"A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function","volume":"17","author":"CA Rubel","year":"2016","journal-title":"Cell Rep"},{"issue":"1","key":"pgen.1009986.ref108","doi-asserted-by":"crossref","first-page":"4421","DOI":"10.1038\/s41467-018-06652-w","article-title":"SOX17 regulates uterine epithelial-stromal cross-talk acting via a distal enhancer upstream of Ihh.","volume":"9","author":"X Wang","year":"2018","journal-title":"Nat Commun."},{"issue":"1","key":"pgen.1009986.ref109","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.canlet.2007.12.011","article-title":"p63 contributes to cell invasion and migration in squamous cell carcinoma of the head and neck","volume":"263","author":"X Gu","year":"2008","journal-title":"Cancer Lett"},{"issue":"5","key":"pgen.1009986.ref110","doi-asserted-by":"crossref","first-page":"a001883","DOI":"10.1101\/cshperspect.a001883","article-title":"Tumor suppressive functions of p53.","volume":"1","author":"JT Zilfou","year":"2009","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"51","key":"pgen.1009986.ref111","doi-asserted-by":"crossref","first-page":"20380","DOI":"10.1073\/pnas.0810485105","article-title":"Highly parallel identification of essential genes in cancer cells","volume":"105","author":"B Luo","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"pgen.1009986.ref112","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1073\/pnas.1804858116","article-title":"Arid1a is essential for intestinal stem cells through Sox9 regulation","volume":"116","author":"Y Hiramatsu","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pgen.1009986.ref113","doi-asserted-by":"crossref","first-page":"4067","DOI":"10.1038\/s41467-019-12037-4","article-title":"ARID1A promotes genomic stability through protecting telomere cohesion.","volume":"10","author":"B Zhao","year":"2019","journal-title":"Nat Commun."},{"issue":"1","key":"pgen.1009986.ref114","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ccr.2005.12.013","article-title":"p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis","volume":"9","author":"JW Rocco","year":"2006","journal-title":"Cancer Cell"},{"issue":"1","key":"pgen.1009986.ref115","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/cdd.2017.169","article-title":"How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression?","volume":"25","author":"BJ Aubrey","year":"2018","journal-title":"Cell Death Differ"},{"issue":"12","key":"pgen.1009986.ref116","doi-asserted-by":"crossref","first-page":"3460","DOI":"10.1016\/j.bbamcr.2013.06.028","article-title":"ER stress-induced cell death mechanisms","volume":"1833","author":"R Sano","year":"2013","journal-title":"Biochim Biophys Acta"},{"issue":"11","key":"pgen.1009986.ref117","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.tcb.2020.09.002","article-title":"When Endoplasmic Reticulum Proteostasis Meets the DNA Damage Response","volume":"30","author":"M Gonzalez-Quiroz","year":"2020","journal-title":"Trends Cell Biol"},{"issue":"1","key":"pgen.1009986.ref118","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1038\/s41467-020-16416-0","article-title":"Inactivation of Arid1a in the endometrium is associated with endometrioid tumorigenesis through transcriptional reprogramming.","volume":"11","author":"Y Suryo Rahmanto","year":"2020","journal-title":"Nat Commun."},{"issue":"5","key":"pgen.1009986.ref119","doi-asserted-by":"crossref","first-page":"699","DOI":"10.4161\/cbt.7.5.5712","article-title":"Analysis of p53 mutation status in human cancer cell lines: a paradigm for cell line cross-contamination","volume":"7","author":"H Berglind","year":"2008","journal-title":"Cancer Biol Ther"},{"issue":"12B","key":"pgen.1009986.ref120","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1101\/gad.5.12b.2375","article-title":"p53 alteration is a common event in the spontaneous immortalization of primary BALB\/c murine embryo fibroblasts","volume":"5","author":"DM Harvey","year":"1991","journal-title":"Genes Dev"},{"issue":"1","key":"pgen.1009986.ref121","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1006\/scbi.2000.0342","article-title":"Cellular transformation by SV40 large T antigen: interaction with host proteins","volume":"11","author":"SH Ali","year":"2001","journal-title":"Semin Cancer Biol"},{"issue":"7757","key":"pgen.1009986.ref122","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41586-019-1186-3","article-title":"Next-generation characterization of the Cancer Cell Line Encyclopedia","volume":"569","author":"M Ghandi","year":"2019","journal-title":"Nature"},{"issue":"1","key":"pgen.1009986.ref123","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"A Dobin","year":"2013","journal-title":"Bioinformatics"},{"issue":"12","key":"pgen.1009986.ref124","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"issue":"7","key":"pgen.1009986.ref125","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nmeth.3885","article-title":"Data-driven hypothesis weighting increases detection power in genome-scale multiple testing.","volume":"13","author":"N Ignatiadis","year":"2016","journal-title":"Nat Methods."},{"key":"pgen.1009986.ref126","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"M. Martin","year":"2011","journal-title":"EMBnet J"},{"key":"pgen.1009986.ref127","unstructured":"Andrews S. FastQC: A Quality Control Tool for High Throughput Sequence Data. 2010. Available from: http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc."},{"issue":"4","key":"pgen.1009986.ref128","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2.","volume":"9","author":"B Langmead","year":"2012","journal-title":"Nat Methods."},{"issue":"16","key":"pgen.1009986.ref129","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"issue":"9","key":"pgen.1009986.ref130","doi-asserted-by":"crossref","first-page":"R137","DOI":"10.1186\/gb-2008-9-9-r137","article-title":"Model-based analysis of ChIP-Seq (MACS).","volume":"9","author":"Y Zhang","year":"2008","journal-title":"Genome Biol"},{"issue":"1","key":"pgen.1009986.ref131","doi-asserted-by":"crossref","first-page":"9354","DOI":"10.1038\/s41598-019-45839-z","article-title":"The ENCODE Blacklist: Identification of Problematic Regions of the Genome.","volume":"9","author":"HM Amemiya","year":"2019","journal-title":"Sci Rep"},{"issue":"6","key":"pgen.1009986.ref132","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features","volume":"26","author":"AR Quinlan","year":"2010","journal-title":"Bioinformatics"},{"issue":"4","key":"pgen.1009986.ref133","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","article-title":"Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities","volume":"38","author":"S Heinz","year":"2010","journal-title":"Mol Cell"},{"issue":"5","key":"pgen.1009986.ref134","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/gkv1191","article-title":"csaw: a Bioconductor package for differential binding analysis of ChIP-seq data using sliding windows","volume":"44","author":"AT Lun","year":"2016","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pgen.1009986.ref135","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nbt.1754","article-title":"Integrative genomics viewer","volume":"29","author":"JT Robinson","year":"2011","journal-title":"Nat Biotechnol"},{"issue":"269","key":"pgen.1009986.ref136","first-page":"pl1","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal","volume":"6","author":"J Gao","year":"2013","journal-title":"Sci Signal"},{"issue":"5","key":"pgen.1009986.ref137","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data","volume":"2","author":"E Cerami","year":"2012","journal-title":"Cancer Discov"},{"issue":"12","key":"pgen.1009986.ref138","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1038\/ng.3984","article-title":"Computational correction of copy number effect improves specificity of CRISPR-Cas9 essentiality screens in cancer cells","volume":"49","author":"RM Meyers","year":"2017","journal-title":"Nat Genet"},{"key":"pgen.1009986.ref139","unstructured":"Depmap B. DepMap 21Q1 Public. 2020."},{"issue":"12","key":"pgen.1009986.ref140","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1056\/NEJMp1607591","article-title":"Toward a Shared Vision for Cancer Genomic Data","volume":"375","author":"RL Grossman","year":"2016","journal-title":"N Engl J Med"},{"key":"pgen.1009986.ref141","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"B Li","year":"2011","journal-title":"BMC Bioinformatics"},{"issue":"7","key":"pgen.1009986.ref142","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"ME Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"1\u20132","key":"pgen.1009986.ref143","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0166-4328(01)00297-2","article-title":"Controlling the false discovery rate in behavior genetics research","volume":"125","author":"Y Benjamini","year":"2001","journal-title":"Behav Brain Res"},{"issue":"D1","key":"pgen.1009986.ref144","doi-asserted-by":"crossref","first-page":"D330","DOI":"10.1093\/nar\/gky1055","article-title":"The Gene Ontology Resource: 20 years and still GOing strong.","volume":"47","author":"The Gene Ontology Consortium","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pgen.1009986.ref145","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology.","volume":"25","author":"The Gene Ontology Consortium.","year":"2000","journal-title":"Nat Genet."},{"issue":"5","key":"pgen.1009986.ref146","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/ng0506-500","article-title":"GenePattern 2.0.","volume":"38","author":"M Reich","year":"2006","journal-title":"Nat Genet"},{"issue":"5","key":"pgen.1009986.ref147","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"G Yu","year":"2012","journal-title":"OMICS"},{"key":"pgen.1009986.ref148","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1471-2164-10-22","article-title":"BioMart\u2014biological queries made easy","volume":"10","author":"D Smedley","year":"2009","journal-title":"BMC Genomics"},{"issue":"18","key":"pgen.1009986.ref149","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Z Gu","year":"2016","journal-title":"Bioinformatics"},{"issue":"1","key":"pgen.1009986.ref150","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1101\/gr.097857.109","article-title":"Detection of nonneutral substitution rates on mammalian phylogenies","volume":"20","author":"KS Pollard","year":"2010","journal-title":"Genome Res"},{"issue":"8","key":"pgen.1009986.ref151","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1101\/gr.3715005","article-title":"Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes","volume":"15","author":"A Siepel","year":"2005","journal-title":"Genome Res"},{"key":"pgen.1009986.ref152","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: Elegant Graphics for Data Analysis:","author":"H. Wickham","year":"2016"},{"key":"pgen.1009986.ref153","unstructured":"R Core Team. R: A language and environment for statistical computing. 2018."}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1009986","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1009986","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T18:39:09Z","timestamp":1641580749000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1009986"}},"subtitle":[],"editor":[{"given":"David B.","family":"Chapel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,12,23]]},"references-count":153,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1009986","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pgen.1009986","asserted-by":"object"}]},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,23]]}}}