{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:06:28Z","timestamp":1792263988927,"version":"4.4.0"},"reference-count":70,"publisher":"American Association for Cancer Research (AACR)","issue":"10","funder":[{"DOI":"10.13039\/501100001677","name":"Inserm","doi-asserted-by":"crossref","award":["UMR 1138"],"award-info":[{"award-number":["UMR 1138"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001677","name":"Inserm","doi-asserted-by":"crossref","award":["UMR 938"],"award-info":[{"award-number":["UMR 938"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001677","name":"Inserm","doi-asserted-by":"crossref","award":["UMR 830"],"award-info":[{"award-number":["UMR 830"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Pediatric liver cancers (PLC) comprise diverse diseases affecting infants, children, and adolescents. Despite overall good prognosis, PLCs display heterogeneous response to chemotherapy. Integrated genomic analysis of 126 pediatric liver tumors showed a continuum of driver mechanisms associated with patient age, including new targetable oncogenes. In 10% of patients with hepatoblastoma, all before three years old, we identified a mosaic premalignant clonal expansion of cells altered at the 11p15.5 locus. Analysis of spatial and longitudinal heterogeneity revealed an important plasticity between \u201chepatocytic,\u201d \u201cliver progenitor,\u201d and \u201cmesenchymal\u201d molecular subgroups of hepatoblastoma. We showed that during chemotherapy, \u201cliver progenitor\u201d cells accumulated massive loads of cisplatin-induced mutations with a specific mutational signature, leading to the development of heavily mutated relapses and metastases. Drug screening in PLC cell lines identified promising targets for cisplatin-resistant progenitor cells, validated in mouse xenograft experiments. These data provide new insights into cisplatin resistance mechanisms in PLC and suggest alternative therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>PLCs are deadly when they resist chemotherapy, with limited alternative treatment options. Using a multiomics approach, we identified PLC driver genes and the cellular phenotype at the origin of cisplatin resistance. We validated new treatments targeting these molecular features in cell lines and xenografts.<\/jats:p>\n                    <jats:p>This article is highlighted in the In This Issue feature, p. 2355<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-20-1809","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T18:01:06Z","timestamp":1619200866000},"page":"2524-2543","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Integrated Genomic Analysis Identifies Driver Genes and Cisplatin-Resistant Progenitor Phenotype in Pediatric Liver Cancer"],"prefix":"10.1158","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4428-2997","authenticated-orcid":false,"given":"Theo Z.","family":"Hirsch","sequence":"first","affiliation":[{"name":"1Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, INSERM, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Pilet","sequence":"additional","affiliation":[{"name":"1Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, INSERM, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Morcrette","sequence":"additional","affiliation":[{"name":"1Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, INSERM, Paris, France."},{"name":"2Department of Pediatric Pathology, APHP, Robert Debr\u00e9 Hospital, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1120-4151","authenticated-orcid":false,"given":"Am\u00e9lie","family":"Roehrig","sequence":"additional","affiliation":[{"name":"1Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, INSERM, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedict J.E.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"1Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, INSERM, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Molina","sequence":"additional","affiliation":[{"name":"1Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, INSERM, Paris, France."},{"name":"3Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9270-2015","authenticated-orcid":false,"given":"Quentin","family":"Bayard","sequence":"additional","affiliation":[{"name":"1Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, INSERM, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0475-3934","authenticated-orcid":false,"given":"Eric","family":"Tr\u00e9po","sequence":"additional","affiliation":[{"name":"1Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, INSERM, Paris, France."},{"name":"4Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, C.U.B. H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles, Brussels, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1855-7467","authenticated-orcid":false,"given":"L\u00e9a","family":"Meunier","sequence":"additional","affiliation":[{"name":"1Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, INSERM, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6319-3642","authenticated-orcid":false,"given":"Stefano","family":"Caruso","sequence":"additional","affiliation":[{"name":"1Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, INSERM, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Renault","sequence":"additional","affiliation":[{"name":"5Laboratory for Bioinformatics, Fondation Jean Dausset\u2013CEPH, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Deleuze","sequence":"additional","affiliation":[{"name":"5Laboratory for Bioinformatics, Fondation Jean Dausset\u2013CEPH, Paris, France."},{"name":"6Universit\u00e9 Paris-Saclay, Commissariat \u00e0 l\u2019\u00c9nergie Atomique et aux \u00c9nergies Alternatives, Centre National de Recherche en G\u00e9nomique Humaine, Evry, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7603-7828","authenticated-orcid":false,"given":"Brice","family":"Fresneau","sequence":"additional","affiliation":[{"name":"7Gustave Roussy, Universit\u00e9 Paris-Saclay, Department of Children and Adolescents Oncology, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Chardot","sequence":"additional","affiliation":[{"name":"8Universit\u00e9 de Paris, APHP, Necker Hospital, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Gonzales","sequence":"additional","affiliation":[{"name":"9Pediatric Hepatology and Liver Transplantation Unit, National Reference Centre for Rare Pediatric Liver Diseases, FILFOIE, ERN RARE LIVER, APHP, Bic\u00eatre University Hospital, University of Paris-Saclay, Le Kremlin Bic\u00eatre, and INSERM UMR_S 1193, Hepatinov, University of Paris-Saclay, Orsay, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Jacquemin","sequence":"additional","affiliation":[{"name":"9Pediatric Hepatology and Liver Transplantation Unit, National Reference Centre for Rare Pediatric Liver Diseases, FILFOIE, ERN RARE LIVER, APHP, Bic\u00eatre University Hospital, University of Paris-Saclay, Le Kremlin Bic\u00eatre, and INSERM UMR_S 1193, Hepatinov, University of Paris-Saclay, Orsay, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3487-3745","authenticated-orcid":false,"given":"Florent","family":"Guerin","sequence":"additional","affiliation":[{"name":"10Department of Pediatric Surgery, Bic\u00eatre Hospital, APHP, Paris-Saclay University, Orsay, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Fabre","sequence":"additional","affiliation":[{"name":"11Department of Pathology, H\u00f4pital Universitaire Necker-Enfants malades, AP-HP, Centre\u2013Universit\u00e9 de Paris, Universit\u00e9 Paris Descartes, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Aerts","sequence":"additional","affiliation":[{"name":"12Oncology Center SIREDO, Institut Curie, PSL Research University, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Taque","sequence":"additional","affiliation":[{"name":"13D\u00e9partement de P\u00e9diatrie, CHU Fontenoy, Rennes, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Laithier","sequence":"additional","affiliation":[{"name":"14Department of Children Oncology, Centre Hospitalier Universitaire Besan\u00e7on, Besan\u00e7on, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Branchereau","sequence":"additional","affiliation":[{"name":"15Department of Pediatric Surgery, Bic\u00eatre Hospital, APHP, Paris-Saclay University, Orsay, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Guettier","sequence":"additional","affiliation":[{"name":"16Department of Pathology H\u00f4pital Bic\u00eatre\u2013AP-HP, INSERM U1193, Paris-Saclay University, Orsay, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Brugi\u00e8res","sequence":"additional","affiliation":[{"name":"7Gustave Roussy, Universit\u00e9 Paris-Saclay, Department of Children and Adolescents Oncology, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Rebouissou","sequence":"additional","affiliation":[{"name":"1Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, INSERM, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6369-2839","authenticated-orcid":false,"given":"Eric","family":"Letouz\u00e9","sequence":"additional","affiliation":[{"name":"1Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, INSERM, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5687-0334","authenticated-orcid":false,"given":"Jessica","family":"Zucman-Rossi","sequence":"additional","affiliation":[{"name":"1Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, INSERM, Paris, France."},{"name":"17H\u00f4pital Europ\u00e9en Georges Pompidou, Assistance Publique H\u00f4pitaux de Paris, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1086","published-online":{"date-parts":[[2021,4,23]]},"reference":[{"key":"2022060711453244800_bib1","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1053\/jhep.2003.50375","article-title":"Epidemiology of primary hepatic malignancies in U.S. children","volume":"38","author":"Darbari","year":"2003","journal-title":"Hepatology"},{"key":"2022060711453244800_bib2","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.cld.2011.03.011","article-title":"Liver neoplasia in children","volume":"15","author":"Hadzic","year":"2011","journal-title":"Clin Liver Dis"},{"key":"2022060711453244800_bib3","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1002\/gcc.20770","article-title":"Genome-wide analysis of allelic imbalances reveals 4q deletions as a poor prognostic factor and MDM4 amplification at 1q32.1 in hepatoblastoma","volume":"49","author":"Arai","year":"2010","journal-title":"Genes Chromosomes Cancer"},{"key":"2022060711453244800_bib4","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1016\/j.jhep.2014.08.009","article-title":"The genomic landscape of hepatoblastoma and their progenies with HCC-like features","volume":"61","author":"Eichenm\u00fcller","year":"2014","journal-title":"J Hepatol"},{"key":"2022060711453244800_bib5","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1002\/hep.27243","article-title":"Exome sequencing of hepatoblastoma reveals novel mutations and cancer genes in the Wnt pathway and ubiquitin ligase complex","volume":"60","author":"Jia","year":"2014","journal-title":"Hepatology"},{"key":"2022060711453244800_bib6","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/hep.28888","article-title":"Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups","volume":"65","author":"Sumazin","year":"2017","journal-title":"Hepatology"},{"key":"2022060711453244800_bib7","first-page":"1","article-title":"Integrated multiomics analysis of hepatoblastoma unravels its heterogeneity and provides novel druggable targets.","volume":"4","author":"Sekiguchi","year":"2020","journal-title":"NPJ Precis Oncol"},{"key":"2022060711453244800_bib8","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nature25480","article-title":"The landscape of genomic alterations across childhood cancers","volume":"555","author":"Gr\u00f6bner","year":"2018","journal-title":"Nature"},{"key":"2022060711453244800_bib9","doi-asserted-by":"crossref","first-page":"3980","DOI":"10.3748\/wjg.v24.i35.3980","article-title":"Pediatric hepatocellular carcinoma","volume":"24","author":"Khanna","year":"2018","journal-title":"World J Gastroenterol"},{"key":"2022060711453244800_bib10","doi-asserted-by":"crossref","first-page":"3850","DOI":"10.1038\/ncomms4850","article-title":"Massive gene amplification drives paediatric hepatocellular carcinoma caused by bile salt export pump deficiency","volume":"5","author":"Iannelli","year":"2014","journal-title":"Nat Commun"},{"key":"2022060711453244800_bib11","doi-asserted-by":"crossref","first-page":"e27745","DOI":"10.1002\/pbc.27745","article-title":"Characterization of pediatric hepatocellular carcinoma reveals genomic heterogeneity and diverse signaling pathway activation","volume":"66","author":"Haines","year":"2019","journal-title":"Pediatr Blood Cancer"},{"key":"2022060711453244800_bib12","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1126\/science.1249484","article-title":"Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma","volume":"343","author":"Honeyman","year":"2014","journal-title":"Science"},{"key":"2022060711453244800_bib13","doi-asserted-by":"crossref","first-page":"215064","DOI":"10.1155\/2013\/215064","article-title":"Benign hepatocellular tumors in children: focal nodular hyperplasia and hepatocellular adenoma","volume":"2013","author":"Franchi-Abella","year":"2013","journal-title":"Int J Hepatol"},{"key":"2022060711453244800_bib14","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/modpathol.2013.80","article-title":"Towards an international pediatric liver tumor consensus classification: proceedings of the Los Angeles COG liver tumors symposium","volume":"27","author":"L\u00f3pez-Terrada","year":"2014","journal-title":"Mod Pathol"},{"key":"2022060711453244800_bib15","doi-asserted-by":"crossref","first-page":"555","DOI":"10.21037\/atm.2019.09.76","article-title":"Survival and analysis of prognostic factors for hepatoblastoma: based on SEER database","volume":"7","author":"Feng","year":"2019","journal-title":"Ann Transl Med"},{"key":"2022060711453244800_bib16","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.jhep.2020.03.025","article-title":"Epigenetic footprint enables molecular risk stratification of hepatoblastoma with clinical implications","volume":"73","author":"Carrillo-Reixach","year":"2020","journal-title":"J Hepatol"},{"key":"2022060711453244800_bib17","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"2022060711453244800_bib18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","article-title":"The repertoire of mutational signatures in human cancer","volume":"578","author":"Alexandrov","year":"2020","journal-title":"Nature"},{"key":"2022060711453244800_bib19","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/path.4880","article-title":"Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas","volume":"242","author":"Pilati","year":"2017","journal-title":"J Pathol"},{"key":"2022060711453244800_bib20","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1101\/gr.230219.117","article-title":"In-depth characterization of the cisplatin mutational signature in human cell lines and in esophageal and liver tumors","volume":"28","author":"Boot","year":"2018","journal-title":"Genome Res"},{"key":"2022060711453244800_bib21","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1038\/onc.2011.384","article-title":"Molecular mechanisms of cisplatin resistance","volume":"31","author":"Galluzzi","year":"2012","journal-title":"Oncogene"},{"key":"2022060711453244800_bib22","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1053\/j.gastro.2016.09.001","article-title":"IGF2 is up-regulated by epigenetic mechanisms in hepatocellular carcinomas and is an actionable oncogene product in experimental models","volume":"151","author":"Martinez-Quetglas","year":"2016","journal-title":"Gastroenterology"},{"key":"2022060711453244800_bib23","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1053\/j.gastro.2019.05.001","article-title":"Analysis of liver cancer cell lines identifies agents with likely efficacy against hepatocellular carcinoma and markers of response","volume":"157","author":"Caruso","year":"2019","journal-title":"Gastroenterology"},{"key":"2022060711453244800_bib24","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1158\/2159-8290.CD-17-0321","article-title":"Accelerating discovery of functional mutant alleles in cancer","volume":"8","author":"Chang","year":"2018","journal-title":"Cancer Discov"},{"key":"2022060711453244800_bib25","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1126\/science.aax1323","article-title":"Embryonal precursors of Wilms tumor","volume":"366","author":"Coorens","year":"2019","journal-title":"Science"},{"key":"2022060711453244800_bib26","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.ccr.2008.11.002","article-title":"Hepatic stem-like phenotype and interplay of Wnt\/beta-catenin and Myc signaling in aggressive childhood liver cancer","volume":"14","author":"Cairo","year":"2008","journal-title":"Cancer Cell"},{"key":"2022060711453244800_bib27","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/hep.29672","article-title":"New insights into diagnosis and therapeutic options for proliferative hepatoblastoma","volume":"68","author":"Hooks","year":"2018","journal-title":"Hepatology"},{"key":"2022060711453244800_bib28","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/nature22973","article-title":"The whole-genome landscape of medulloblastoma subtypes","volume":"547","author":"Northcott","year":"2017","journal-title":"Nature"},{"key":"2022060711453244800_bib29","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1038\/ng.3899","article-title":"Neuroblastoma is composed of two super-enhancer-associated differentiation states","volume":"49","author":"van Groningen","year":"2017","journal-title":"Nat Genet"},{"key":"2022060711453244800_bib30","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1038\/ng.3921","article-title":"Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries","volume":"49","author":"Boeva","year":"2017","journal-title":"Nat Genet"},{"key":"2022060711453244800_bib31","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1038\/s41467-017-01358-x","article-title":"Mutational signatures reveal the dynamic interplay of risk factors and cellular processes during liver tumorigenesis","volume":"8","author":"Letouz\u00e9","year":"2017","journal-title":"Nat Commun"},{"key":"2022060711453244800_bib32","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1038\/s41588-019-0525-5","article-title":"The mutational footprints of cancer therapies","volume":"51","author":"Pich","year":"2019","journal-title":"Nat Genet"},{"key":"2022060711453244800_bib33","doi-asserted-by":"crossref","first-page":"e1583547","DOI":"10.1080\/2162402X.2019.1583547","article-title":"APC germline hepatoblastomas demonstrate cisplatin-induced intratumor tertiary lymphoid structures","volume":"8","author":"Morcrette","year":"2019","journal-title":"Oncoimmunology"},{"key":"2022060711453244800_bib34","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/onc.2009.356","article-title":"Immunogenic death of colon cancer cells treated with oxaliplatin","volume":"29","author":"Tesniere","year":"2010","journal-title":"Oncogene"},{"key":"2022060711453244800_bib35","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2022060711453244800_bib36","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res"},{"key":"2022060711453244800_bib37","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat Genet"},{"key":"2022060711453244800_bib38","doi-asserted-by":"crossref","first-page":"11.10.1","DOI":"10.1002\/0471250953.bi1110s43","article-title":"From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline","volume":"43","author":"Van der Auwera","year":"2013","journal-title":"Curr Protoc Bioinformatics"},{"key":"2022060711453244800_bib39","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","article-title":"The ensembl variant effect predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol"},{"key":"2022060711453244800_bib40","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"2022060711453244800_bib41","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nbt.1754","article-title":"Integrative genomics viewer","volume":"29","author":"Robinson","year":"2011","journal-title":"Nat Biotechnol"},{"key":"2022060711453244800_bib42","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1093\/bioinformatics\/btv710","article-title":"Manta: rapid detection of structural variants and indels for germline and cancer sequencing applications","volume":"32","author":"Chen","year":"2016","journal-title":"Bioinformatics"},{"key":"2022060711453244800_bib43","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.cell.2012.04.023","article-title":"The life history of 21 breast cancers","volume":"149","author":"Nik-Zainal","year":"2012","journal-title":"Cell"},{"key":"2022060711453244800_bib44","doi-asserted-by":"crossref","first-page":"R128","DOI":"10.1186\/gb-2009-10-11-r128","article-title":"Genome Alteration Print (GAP): a tool to visualize and mine complex cancer genomic profiles obtained by SNP arrays","volume":"10","author":"Popova","year":"2009","journal-title":"Genome Biol"},{"key":"2022060711453244800_bib45","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1093\/biostatistics\/kxh008","article-title":"Circular binary segmentation for the analysis of array-based DNA copy number data","volume":"5","author":"Olshen","year":"2004","journal-title":"Biostatistics"},{"key":"2022060711453244800_bib46","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/ng.3252","article-title":"Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets","volume":"47","author":"Schulze","year":"2015","journal-title":"Nat Genet"},{"key":"2022060711453244800_bib47","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nature12213","article-title":"Mutational heterogeneity in cancer and the search for new cancer-associated genes","volume":"499","author":"Lawrence","year":"2013","journal-title":"Nature"},{"key":"2022060711453244800_bib48","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s13059-016-0994-0","article-title":"OncodriveFML: a general framework to identify coding and non-coding regions with cancer driver mutations","volume":"17","author":"Mularoni","year":"2016","journal-title":"Genome Biol"},{"key":"2022060711453244800_bib49","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nature25795","article-title":"Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours","volume":"555","author":"Ma","year":"2018","journal-title":"Nature"},{"key":"2022060711453244800_bib50","doi-asserted-by":"crossref","first-page":"3380","DOI":"10.1093\/bioinformatics\/bty388","article-title":"Palimpsest: an R package for studying mutational and structural variant signatures along clonal evolution in cancer","volume":"34","author":"Shinde","year":"2018","journal-title":"Bioinformatics"},{"key":"2022060711453244800_bib51","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/nm.3886","article-title":"Subclonal diversification of primary breast cancer revealed by multiregion sequencing","volume":"21","author":"Yates","year":"2015","journal-title":"Nat Med"},{"key":"2022060711453244800_bib52","doi-asserted-by":"crossref","first-page":"R36","DOI":"10.1186\/gb-2013-14-4-r36","article-title":"TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions","volume":"14","author":"Kim","year":"2013","journal-title":"Genome Biol"},{"key":"2022060711453244800_bib53","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2013a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"2022060711453244800_bib54","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":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"2022060711453244800_bib55","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s13059-019-1842-9","article-title":"Accuracy assessment of fusion transcript detection via read-mapping and de novo fusion transcript assembly-based methods","volume":"20","author":"Haas","year":"2019","journal-title":"Genome Biol"},{"key":"2022060711453244800_bib56","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":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2022060711453244800_bib57","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/s13059-016-1070-5","article-title":"Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression","volume":"17","author":"Becht","year":"2016","journal-title":"Genome Biol"},{"key":"2022060711453244800_bib58","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1038\/s41591-020-0844-1","article-title":"A single-cell and single-nucleus RNA-Seq toolbox for fresh and frozen human tumors","volume":"26","author":"Slyper","year":"2020","journal-title":"Nat Med"},{"key":"2022060711453244800_bib59","doi-asserted-by":"crossref","first-page":"14049","DOI":"10.1038\/ncomms14049","article-title":"Massively parallel digital transcriptional profiling of single cells","volume":"8","author":"Zheng","year":"2017","journal-title":"Nat Commun"},{"key":"2022060711453244800_bib60","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"2022060711453244800_bib61","first-page":"468","article-title":"Preparation of reduced representation bisulfite sequencing libraries for genome-scale DNA methylation profiling. Nature Protocols","volume":"6","author":"Gu","year":"2011","journal-title":"Nature"},{"key":"2022060711453244800_bib62","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1186\/1471-2164-14-774","article-title":"BS-Seeker2: a versatile aligning pipeline for bisulfite sequencing data","volume":"14","author":"Guo","year":"2013","journal-title":"BMC Genomics"},{"key":"2022060711453244800_bib63","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1093\/bioinformatics\/btx595","article-title":"CGmapTools improves the precision of heterozygous SNV calls and supports allele-specific methylation detection and visualization in bisulfite-sequencing data","volume":"34","author":"Guo","year":"2018","journal-title":"Bioinformatics"},{"key":"2022060711453244800_bib64","doi-asserted-by":"crossref","first-page":"R87","DOI":"10.1186\/gb-2012-13-10-r87","article-title":"methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles","volume":"13","author":"Akalin","year":"2012","journal-title":"Genome Biol"},{"key":"2022060711453244800_bib65","doi-asserted-by":"crossref","DOI":"10.1002\/hep.31796","article-title":"DNA methylation signatures reveal the diversity of processes remodeling hepatocellular carcinoma methylomes","author":"Meunier","year":"2021","journal-title":"Hepatology"},{"key":"2022060711453244800_bib66","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nature14248","article-title":"Integrative analysis of 111 reference human epigenomes","volume":"518","author":"Roadmap Epigenomics Consortium","year":"2015","journal-title":"Nature"},{"key":"2022060711453244800_bib67","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s13059-018-1510-5","article-title":"A comprehensive analysis of 195 DNA methylomes reveals shared and cell-specific features of partially methylated domains","volume":"19","author":"Salhab","year":"2018","journal-title":"Genome Biol"},{"key":"2022060711453244800_bib68","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature11247","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","author":"ENCODE Project Consortium","year":"2012","journal-title":"Nature"},{"key":"2022060711453244800_bib69","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1093\/bioinformatics\/bty902","article-title":"ELMER v.2: an R\/Bioconductor package to reconstruct gene regulatory networks from DNA methylation and transcriptome profiles","volume":"35","author":"Silva","year":"2019","journal-title":"Bioinformatics"},{"key":"2022060711453244800_bib70","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1038\/ncomms3218","article-title":"High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions","volume":"4","author":"Nault","year":"2013","journal-title":"Nat Commun"}],"container-title":["Cancer Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/11\/10\/2524\/3082426\/2524.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/11\/10\/2524\/3082426\/2524.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T03:31:48Z","timestamp":1724902308000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article\/11\/10\/2524\/665585\/Integrated-Genomic-Analysis-Identifies-Driver"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,23]]},"references-count":70,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,4,23]]},"published-print":{"date-parts":[[2021,10,1]]}},"URL":"https:\/\/doi.org\/10.1158\/2159-8290.cd-20-1809","relation":{"has-preprint":[{"id-type":"doi","id":"10.1158\/2159-8290.c.6549043.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22539283","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22539286","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22539286.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22539283.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.c.6549043","asserted-by":"object"}]},"ISSN":["2159-8274","2159-8290"],"issn-type":[{"value":"2159-8274","type":"print"},{"value":"2159-8290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,23]]}}}