{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T09:23:36Z","timestamp":1781861016139,"version":"3.54.5"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"7696","license":[{"start":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T00:00:00Z","timestamp":1519776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T00:00:00Z","timestamp":1519776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2018,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes that are dysregulated in cancer cells from diverse lineages. Pan-cancer analyses have been performed for adult\n                    <jats:sup>1,2,3,4<\/jats:sup>\n                    but not paediatric cancers, which commonly occur in developing mesodermic rather than adult epithelial tissues\n                    <jats:sup>5<\/jats:sup>\n                    . Here we present a pan-cancer study of somatic alterations, including single nucleotide variants, small insertions or deletions, structural variations, copy number alterations, gene fusions and internal tandem duplications in 1,699 paediatric leukaemias and solid tumours across six histotypes, with whole-genome, whole-exome and transcriptome sequencing data processed under a uniform analytical framework. We report 142 driver genes in paediatric cancers, of which only 45% match those found in adult pan-cancer studies; copy number alterations and structural variants constituted the majority (62%) of events. Eleven genome-wide mutational signatures were identified, including one attributed to ultraviolet-light exposure in eight aneuploid leukaemias. Transcription of the mutant allele was detectable for 34% of protein-coding mutations, and 20% exhibited allele-specific expression. These data provide a comprehensive genomic architecture for paediatric cancers and emphasize the need for paediatric cancer-specific development of precision therapies.\n                  <\/jats:p>","DOI":"10.1038\/nature25795","type":"journal-article","created":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T05:21:34Z","timestamp":1519795294000},"page":"371-376","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":839,"title":["Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours"],"prefix":"10.1038","volume":"555","author":[{"given":"Xiaotu","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmil B.","family":"Alexandrov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael N.","family":"Edmonson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Gawad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Rusch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Easton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Huether","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Gonzalez-Pena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Wilkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro C.","family":"Hermida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Sioson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Pounds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyuan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda E.","family":"Ries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J.","family":"Diskin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm A.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime M.","family":"Guidry Auvil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Meltzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching C.","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Perlman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Maris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soheil","family":"Meshinchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Hunger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela S.","family":"Gerhard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,2,28]]},"reference":[{"key":"BFnature25795_CR1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nature12634","volume":"502","author":"C Kandoth","year":"2013","unstructured":"Kandoth, C . et al. Mutational landscape and significance across 12 major cancer types. Nature 502, 333\u2013339 (2013)","journal-title":"Nature"},{"key":"BFnature25795_CR2","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nature12912","volume":"505","author":"MS Lawrence","year":"2014","unstructured":"Lawrence, M. S . et al. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505, 495\u2013501 (2014)","journal-title":"Nature"},{"key":"BFnature25795_CR3","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/ng.3168","volume":"47","author":"MD Leiserson","year":"2015","unstructured":"Leiserson, M. D . et al. Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes. Nat. Genet. 47, 106\u2013114 (2015)","journal-title":"Nat. Genet."},{"key":"BFnature25795_CR4","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1038\/ng.2760","volume":"45","author":"TI Zack","year":"2013","unstructured":"Zack, T. I . et al. Pan-cancer patterns of somatic copy number alteration. Nat. Genet. 45, 1134\u20131140 (2013)","journal-title":"Nat. Genet."},{"key":"BFnature25795_CR5","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/ng.2287","volume":"44","author":"JR Downing","year":"2012","unstructured":"Downing, J. R . et al. The Pediatric Cancer Genome Project. Nat. Genet. 44, 619\u2013622 (2012)","journal-title":"Nat. Genet."},{"key":"BFnature25795_CR6","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","volume":"500","author":"LB Alexandrov","year":"2013","unstructured":"Alexandrov, L. B . et al. Signatures of mutational processes in human cancer. Nature 500, 415\u2013421 (2013)","journal-title":"Nature"},{"key":"BFnature25795_CR7","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1126\/science.aad7363","volume":"350","author":"LB Alexandrov","year":"2015","unstructured":"Alexandrov, L. B. Understanding the origins of human cancer. Science 350, 1175\u20131177 (2015)","journal-title":"Science"},{"key":"BFnature25795_CR8","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nature22071","volume":"545","author":"NK Hayward","year":"2017","unstructured":"Hayward, N. K . et al. Whole-genome landscapes of major melanoma subtypes. Nature 545, 175\u2013180 (2017)","journal-title":"Nature"},{"key":"BFnature25795_CR9","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/jid.2014.425","volume":"135","author":"C Lu","year":"2015","unstructured":"Lu, C . et al. The genomic landscape of childhood and adolescent melanoma. J. Invest. Dermatol. 135, 816\u2013823 (2015)","journal-title":"J. Invest. Dermatol."},{"key":"BFnature25795_CR10","doi-asserted-by":"crossref","first-page":"3904","DOI":"10.1073\/pnas.90.9.3904","volume":"90","author":"TM Reid","year":"1993","unstructured":"Reid, T. M. & Loeb, L. A. Tandem double CC--&gt;TT mutations are produced by reactive oxygen species. Proc. Natl Acad. Sci. USA 90, 3904\u20133907 (1993)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature25795_CR11","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0027-5107(99)00075-5","volume":"427","author":"TG Newcomb","year":"1999","unstructured":"Newcomb, T. G ., Allen, K. J ., Tkeshelashvili, L . & Loeb, L. A. Detection of tandem CC--&gt;TT mutations induced by oxygen radicals using mutation-specific PCR. Mutat. Res. 427, 21\u201330 (1999)","journal-title":"Mutat. Res."},{"key":"BFnature25795_CR12","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1093\/bioinformatics\/btt372","volume":"29","author":"S Pounds","year":"2013","unstructured":"Pounds, S . et al. A genomic random interval model for statistical analysis of genomic lesion data. Bioinformatics 29, 2088\u20132095 (2013)","journal-title":"Bioinformatics"},{"key":"BFnature25795_CR13","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nature12213","volume":"499","author":"MS Lawrence","year":"2013","unstructured":"Lawrence, M. S . et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499, 214\u2013218 (2013)","journal-title":"Nature"},{"key":"BFnature25795_CR14","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1158\/2159-8290.CD-14-0622","volume":"4","author":"F Tirode","year":"2014","unstructured":"Tirode, F . et al. Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations. Cancer Discov. 4, 1342\u20131353 (2014)","journal-title":"Cancer Discov."},{"key":"BFnature25795_CR15","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1056\/NEJMoa1301689","volume":"368","author":"TJ Ley","year":"2013","unstructured":"Ley, T. J . et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med. 368, 2059\u20132074 (2013)","journal-title":"N. Engl. J. Med."},{"key":"BFnature25795_CR16","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nrc1299","volume":"4","author":"PA Futreal","year":"2004","unstructured":"Futreal, P. A . et al. A census of human cancer genes. Nat. Rev. Cancer 4, 177\u2013183 (2004)","journal-title":"Nat. Rev. Cancer"},{"key":"BFnature25795_CR17","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/ng1364","volume":"36","author":"ID Krantz","year":"2004","unstructured":"Krantz, I. D . et al. Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B. Nat. Genet. 36, 631\u2013635 (2004)","journal-title":"Nat. Genet."},{"key":"BFnature25795_CR18","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/ng1363","volume":"36","author":"ET Tonkin","year":"2004","unstructured":"Tonkin, E. T ., Wang, T. J ., Lisgo, S ., Bamshad, M. J. & Strachan, T. NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome. Nat. Genet. 36, 636\u2013641 (2004)","journal-title":"Nat. Genet."},{"key":"BFnature25795_CR19","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1073\/pnas.0712384105","volume":"105","author":"TD Barber","year":"2008","unstructured":"Barber, T. D . et al. Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers. Proc. Natl Acad. Sci. USA 105, 3443\u20133448 (2008)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature25795_CR20","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/ng1453","volume":"36","author":"J Hellemans","year":"2004","unstructured":"Hellemans, J . et al. Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke\u2013Ollendorff syndrome and melorheostosis. Nat. Genet. 36, 1213\u20131218 (2004)","journal-title":"Nat. Genet."},{"key":"BFnature25795_CR21","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/ng.3909","volume":"49","author":"Y Liu","year":"2017","unstructured":"Liu, Y . et al. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat. Genet. 49, 1211\u20131218 (2017)","journal-title":"Nat. Genet."},{"key":"BFnature25795_CR22","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrc3526","volume":"13","author":"NK Cheung","year":"2013","unstructured":"Cheung, N. K. & Dyer, M. A. Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nat. Rev. Cancer 13, 397\u2013411 (2013)","journal-title":"Nat. Rev. Cancer"},{"key":"BFnature25795_CR23","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1056\/NEJMoa1508054","volume":"373","author":"J Zhang","year":"2015","unstructured":"Zhang, J . et al. Germline mutations in predisposition genes in pediatric cancer. N. Engl. J. Med. 373, 2336\u20132346 (2015)","journal-title":"N. Engl. J. Med."},{"key":"BFnature25795_CR24","doi-asserted-by":"crossref","first-page":"4544","DOI":"10.1128\/MCB.22.13.4544-4555.2002","volume":"22","author":"H Mita","year":"2002","unstructured":"Mita, H ., Tsutsui, J ., Takekawa, M ., Witten, E. A. & Saito, H. Regulation of MTK1\/MEKK4 kinase activity by its N-terminal autoinhibitory domain and GADD45 binding. Mol. Cell. Biol. 22, 4544\u20134555 (2002)","journal-title":"Mol. Cell. Biol."},{"key":"BFnature25795_CR25","doi-asserted-by":"crossref","first-page":"3110","DOI":"10.1182\/blood-2014-04-569327","volume":"124","author":"NU Rashid","year":"2014","unstructured":"Rashid, N. U . et al. Differential and limited expression of mutant alleles in multiple myeloma. Blood 124, 3110\u20133117 (2014)","journal-title":"Blood"},{"key":"BFnature25795_CR26","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/nature10933","volume":"486","author":"SP Shah","year":"2012","unstructured":"Shah, S. P . et al. The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature 486, 395\u2013399 (2012)","journal-title":"Nature"},{"key":"BFnature25795_CR27","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.cell.2012.08.024","volume":"150","author":"R Govindan","year":"2012","unstructured":"Govindan, R . et al. Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell 150, 1121\u20131134 (2012)","journal-title":"Cell"},{"key":"BFnature25795_CR28","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/ng.3466","volume":"48","author":"X Zhou","year":"2016","unstructured":"Zhou, X . et al. Exploring genomic alteration in pediatric cancer using ProteinPaint. Nat. Genet. 48, 4\u20136 (2016)","journal-title":"Nat. Genet."},{"key":"BFnature25795_CR29","doi-asserted-by":"publisher","unstructured":"Gr\u00f6bner, S. N . et al. The landscape of genomic alterations across childhood cancers. Nature \n                    https:\/\/doi.org\/10.1038\/nature25480\n                    \n                   (2018)","DOI":"10.1038\/nature25480"},{"key":"BFnature25795_CR30","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/ijc.24320","volume":"125","author":"L Mirabello","year":"2009","unstructured":"Mirabello, L., Troisi, R. J. & Savage, S. A. International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int. J. Cancer 125, 229\u2013234 (2009)","journal-title":"Int. J. Cancer"},{"key":"BFnature25795_CR31","doi-asserted-by":"crossref","first-page":"15936","DOI":"10.1038\/ncomms15936","volume":"8","author":"S Behjati","year":"2017","unstructured":"Behjati, S. et al. Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma. Nat. Commun. 8, 15936 (2017)","journal-title":"Nat. Commun."},{"key":"BFnature25795_CR32","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1056\/NEJMoa0808253","volume":"360","author":"CG Mullighan","year":"2009","unstructured":"Mullighan, C. G. et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N. Engl. J. Med. 360, 470\u2013480 (2009)","journal-title":"N. Engl. J. Med."},{"key":"BFnature25795_CR33","doi-asserted-by":"crossref","first-page":"6604","DOI":"10.1038\/ncomms7604","volume":"6","author":"X Ma","year":"2015","unstructured":"Ma, X. et al. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia. Nat. Commun. 6, 6604 (2015)","journal-title":"Nat. Commun."},{"key":"BFnature25795_CR34","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/nm.4439","volume":"24","author":"H Bolouri","year":"2018","unstructured":"Bolouri, H. et al. The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions. Nat. Med. 24, 103\u2013112 (2018)","journal-title":"Nat. Med."},{"key":"BFnature25795_CR35","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/ng.2529","volume":"45","author":"TJ Pugh","year":"2013","unstructured":"Pugh, T. J. et al. The genetic landscape of high-risk neuroblastoma. Nat. Genet. 45, 279\u2013284 (2013)","journal-title":"Nat. Genet."},{"key":"BFnature25795_CR36","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1038\/ng.3940","volume":"49","author":"S Gadd","year":"2017","unstructured":"Gadd, S. et al. A Children\u2019s Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor. Nat. Genet. 49, 1487\u20131494 (2017)","journal-title":"Nat. Genet."},{"key":"BFnature25795_CR37","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1126\/science.1181498","volume":"327","author":"R Drmanac","year":"2010","unstructured":"Drmanac, R. et al. Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science 327, 78\u201381 (2010)","journal-title":"Science"},{"key":"BFnature25795_CR38","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1089\/cmb.2011.0201","volume":"19","author":"P Carnevali","year":"2012","unstructured":"Carnevali, P. et al. Computational techniques for human genome resequencing using mated gapped reads. J. Comput. Biol. 19, 279\u2013292 (2012)","journal-title":"J. Comput. Biol."},{"key":"BFnature25795_CR39","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nature09004","volume":"465","author":"W Lee","year":"2010","unstructured":"Lee, W. et al. The mutation spectrum revealed by paired genome sequences from a lung cancer patient. Nature 465, 473\u2013477 (2010)","journal-title":"Nature"},{"key":"BFnature25795_CR40","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1101\/gr.229202","volume":"12","author":"WJ Kent","year":"2002","unstructured":"Kent, W. J. BLAT\u2013the BLAST-like alignment tool. Genome Res. 12, 656\u2013664 (2002)","journal-title":"Genome Res."},{"key":"BFnature25795_CR41","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/nmeth.3394","volume":"12","author":"X Chen","year":"2015","unstructured":"Chen, X. et al. CONSERTING: integrating copy-number analysis with structural-variation detection. Nat. Methods 12, 527\u2013530 (2015)","journal-title":"Nat. Methods"},{"key":"BFnature25795_CR42","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.celrep.2014.03.003","volume":"7","author":"X Chen","year":"2014","unstructured":"Chen, X. et al. Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma. Cell Rep. 7, 104\u2013112 (2014)","journal-title":"Cell Rep."},{"key":"BFnature25795_CR43","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1093\/bioinformatics\/btr032","volume":"27","author":"MN Edmonson","year":"2011","unstructured":"Edmonson, M. N. et al. Bambino: a variant detector and alignment viewer for next-generation sequencing data in the SAM\/BAM format. Bioinformatics 27, 865\u2013866 (2011)","journal-title":"Bioinformatics"},{"key":"BFnature25795_CR44","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/nature10725","volume":"481","author":"J Zhang","year":"2012","unstructured":"Zhang, J. et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 481, 157\u2013163 (2012)","journal-title":"Nature"},{"key":"BFnature25795_CR45","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nature10733","volume":"481","author":"J Zhang","year":"2012","unstructured":"Zhang, J. et al. A novel retinoblastoma therapy from genomic and epigenetic analyses. Nature 481, 329\u2013334 (2012)","journal-title":"Nature"},{"key":"BFnature25795_CR46","doi-asserted-by":"crossref","first-page":"e67","DOI":"10.1093\/nar\/gks1443","volume":"41","author":"M Costello","year":"2013","unstructured":"Costello, M. et al. Discovery and characterization of artifactual mutations in deep coverage targeted capture sequencing data due to oxidative DNA damage during sample preparation. Nucleic Acids Res. 41, e67 (2013)","journal-title":"Nucleic Acids Res."},{"key":"BFnature25795_CR47","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1056\/NEJMoa0903840","volume":"361","author":"ER Mardis","year":"2009","unstructured":"Mardis, E. R. et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N. Engl. J. Med. 361, 1058\u20131066 (2009)","journal-title":"N. Engl. J. Med."},{"key":"BFnature25795_CR48","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.celrep.2012.12.008","volume":"3","author":"LB Alexandrov","year":"2013","unstructured":"Alexandrov, L. B., Nik-Zainal, S., Wedge, D. C., Campbell, P. J. & Stratton, M. R. Deciphering signatures of mutational processes operative in human cancer. Cell Rep. 3, 246\u2013259 (2013)","journal-title":"Cell Rep."},{"key":"BFnature25795_CR49","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1038\/ng.3441","volume":"47","author":"LB Alexandrov","year":"2015","unstructured":"Alexandrov, L. B. et al. Clock-like mutational processes in human somatic cells. Nat. Genet. 47, 1402\u20131407 (2015)","journal-title":"Nat. Genet."},{"key":"BFnature25795_CR50","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/ng.2532","volume":"45","author":"L Holmfeldt","year":"2013","unstructured":"Holmfeldt, L. et al. The genomic landscape of hypodiploid acute lymphoblastic leukemia. Nat. Genet. 45, 242\u2013252 (2013)","journal-title":"Nat. Genet."},{"key":"BFnature25795_CR51","doi-asserted-by":"crossref","first-page":"9440","DOI":"10.1073\/pnas.1530509100","volume":"100","author":"JD Storey","year":"2003","unstructured":"Storey, J. D. & Tibshirani, R. Statistical significance for genomewide studies. Proc. Natl Acad. Sci. USA 100, 9440\u20139445 (2003)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature25795_CR52","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1038\/ng.211","volume":"40","author":"MD To","year":"2008","unstructured":"To, M. D. et al. Kras regulatory elements and exon 4A determine mutation specificity in lung cancer. Nat. Genet. 40, 1240\u20131244 (2008)","journal-title":"Nat. Genet."},{"key":"BFnature25795_CR53","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.cellsig.2007.07.012","volume":"20","author":"S Eisenberg","year":"2008","unstructured":"Eisenberg, S. & Henis, Y. I. Interactions of Ras proteins with the plasma membrane and their roles in signaling. Cell. Signal. 20, 31\u201339 (2008)","journal-title":"Cell. Signal."},{"key":"BFnature25795_CR54","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1038\/ncomms3612","volume":"4","author":"K Yoshihara","year":"2013","unstructured":"Yoshihara, K. et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat. Commun. 4, 2612 (2013)","journal-title":"Nat. Commun."},{"key":"BFnature25795_CR55","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nmeth.3337","volume":"12","author":"AM Newman","year":"2015","unstructured":"Newman, A. M. et al. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 12, 453\u2013457 (2015)","journal-title":"Nat. Methods"},{"key":"BFnature25795_CR56","doi-asserted-by":"crossref","first-page":"17947","DOI":"10.1073\/pnas.1420822111","volume":"111","author":"C Gawad","year":"2014","unstructured":"Gawad, C., Koh, W. & Quake, S. R. Dissecting the clonal origins of childhood acute lymphoblastic leukemia by single-cell genomics. Proc. Natl Acad. Sci. USA 111, 17947\u201317952 (2014)","journal-title":"Proc. Natl Acad. Sci. USA"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature25795.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature25795","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/nature25795","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/nature25795.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T14:12:38Z","timestamp":1684419158000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature25795"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,28]]},"references-count":56,"journal-issue":{"issue":"7696","published-print":{"date-parts":[[2018,3,15]]}},"alternative-id":["BFnature25795"],"URL":"https:\/\/doi.org\/10.1038\/nature25795","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.732764229.793546118","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,28]]},"assertion":[{"value":"6 February 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}