{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T04:39:39Z","timestamp":1793939979197,"version":"4.8.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"7779","license":[{"start":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T00:00:00Z","timestamp":1571788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T00:00:00Z","timestamp":1571788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2019,10,24]]},"DOI":"10.1038\/s41586-019-1670-9","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T04:13:16Z","timestamp":1571976796000},"page":"538-542","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":389,"title":["Somatic mutations and clonal dynamics in healthy and cirrhotic human liver"],"prefix":"10.1038","volume":"574","author":[{"given":"Simon F.","family":"Brunner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola D.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke A.","family":"Wylie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Aitken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathijs A.","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pete","family":"Ellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Alder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvette","family":"Hooks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Abascal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Stratton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inigo","family":"Martincorena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Hoare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,23]]},"reference":[{"key":"1670_CR1","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1016\/j.cell.2017.05.046","volume":"169","author":"Cancer Genome Atlas Research Network","year":"2017","unstructured":"Cancer Genome Atlas Research Network. Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell 169, 1327\u20131341 (2017).","journal-title":"Cell"},{"key":"1670_CR2","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/ng.3252","volume":"47","author":"K Schulze","year":"2015","unstructured":"Schulze, K. et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat. Genet. 47, 505\u2013511 (2015).","journal-title":"Nat. Genet."},{"key":"1670_CR3","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1038\/ng.3126","volume":"46","author":"Y Totoki","year":"2014","unstructured":"Totoki, Y. et al. Trans-ancestry mutational landscape of hepatocellular carcinoma genomes. Nat. Genet. 46, 1267\u20131273 (2014).","journal-title":"Nat. Genet."},{"key":"1670_CR4","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1038\/ng.2291","volume":"44","author":"A Fujimoto","year":"2012","unstructured":"Fujimoto, A. et al. Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators. Nat. Genet. 44, 760\u2013764 (2012).","journal-title":"Nat. Genet."},{"key":"1670_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01358-x","volume":"8","author":"E Letouz\u00e9","year":"2017","unstructured":"Letouz\u00e9, E. et al. Mutational signatures reveal the dynamic interplay of risk factors and cellular processes during liver tumorigenesis. Nat. Commun. 8, 1315 (2017).","journal-title":"Nat. Commun."},{"key":"1670_CR6","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1101\/gr.154492.113","volume":"23","author":"Z Kan","year":"2013","unstructured":"Kan, Z. et al. Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma. Genome Res. 23, 1422\u20131433 (2013).","journal-title":"Genome Res."},{"key":"1670_CR7","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/ng.2256","volume":"44","author":"C Guichard","year":"2012","unstructured":"Guichard, C. et al. Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat. Genet. 44, 694\u2013698 (2012).","journal-title":"Nat. Genet."},{"key":"1670_CR8","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/nature19768","volume":"538","author":"F Blokzijl","year":"2016","unstructured":"Blokzijl, F. et al. Tissue-specific mutation accumulation in human adult stem cells during life. Nature 538, 260\u2013264 (2016).","journal-title":"Nature"},{"key":"1670_CR9","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1126\/science.aao4426","volume":"359","author":"MA Lodato","year":"2018","unstructured":"Lodato, M. A. et al. Aging and neurodegeneration are associated with increased mutations in single human neurons. Science 359, 555\u2013559 (2018).","journal-title":"Science"},{"key":"1670_CR10","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/s41586-018-0497-0","volume":"561","author":"H Lee-Six","year":"2018","unstructured":"Lee-Six, H. et al. Population dynamics of normal human blood inferred from somatic mutations. Nature 561, 473\u2013478 (2018).","journal-title":"Nature"},{"key":"1670_CR11","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1126\/science.aaa6806","volume":"348","author":"I Martincorena","year":"2015","unstructured":"Martincorena, I. et al. High burden and pervasive positive selection of somatic mutations in normal human skin. Science 348, 880\u2013886 (2015).","journal-title":"Science"},{"key":"1670_CR12","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1002\/hep.22791","volume":"49","author":"TG Fellous","year":"2009","unstructured":"Fellous, T. G. et al. Locating the stem cell niche and tracing hepatocyte lineages in human liver. Hepatology 49, 1655\u20131663 (2009).","journal-title":"Hepatology"},{"key":"1670_CR13","first-page":"G1260","volume":"276","author":"SH Sigal","year":"1999","unstructured":"Sigal, S. H. et al. Partial hepatectomy-induced polyploidy attenuates hepatocyte replication and activates cell aging events. Am. J. Physiol. 276, G1260\u2013G1272 (1999).","journal-title":"Am. J. Physiol."},{"key":"1670_CR14","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cell.2010.11.055","volume":"144","author":"PJ Stephens","year":"2011","unstructured":"Stephens, P. J. et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144, 27\u201340 (2011).","journal-title":"Cell"},{"key":"1670_CR15","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.ygeno.2014.01.003","volume":"103","author":"J Fernandez-Banet","year":"2014","unstructured":"Fernandez-Banet, J. et al. Decoding complex patterns of genomic rearrangement in hepatocellular carcinoma. Genomics 103, 189\u2013203 (2014).","journal-title":"Genomics"},{"key":"1670_CR16","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/j.cell.2016.12.025","volume":"168","author":"M Imielinski","year":"2017","unstructured":"Imielinski, M., Guo, G. & Meyerson, M. Insertions and deletions target lineage-defining genes in human cancers. Cell 168, 460\u2013472 (2017).","journal-title":"Cell"},{"key":"1670_CR17","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1016\/j.cell.2017.09.042","volume":"171","author":"I Martincorena","year":"2017","unstructured":"Martincorena, I. et al. Universal patterns of selection in cancer and somatic tissues. Cell 171, 1029\u20131041 (2017).","journal-title":"Cell"},{"key":"1670_CR18","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1016\/j.jhep.2017.08.013","volume":"67","author":"S Torrecilla","year":"2017","unstructured":"Torrecilla, S. et al. Trunk mutational events present minimal intra- and inter-tumoral heterogeneity in hepatocellular carcinoma. J. Hepatol. 67, 1222\u20131231 (2017).","journal-title":"J. Hepatol."},{"key":"1670_CR19","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1016\/j.cell.2012.04.023","volume":"149","author":"S Nik-Zainal","year":"2012","unstructured":"Nik-Zainal, S. et al. The life history of 21 breast cancers. Cell 149, 994\u20131007 (2012).","journal-title":"Cell"},{"key":"1670_CR20","doi-asserted-by":"publisher","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":"1670_CR21","doi-asserted-by":"publisher","first-page":"2308","DOI":"10.1016\/j.celrep.2018.11.014","volume":"25","author":"FG Osorio","year":"2018","unstructured":"Osorio, F. G. et al. Somatic mutations reveal lineage relationships and age-related mutagenesis in human hematopoiesis. Cell Rep. 25, 2308\u20132316 (2018).","journal-title":"Cell Rep."},{"key":"1670_CR22","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.cell.2015.12.050","volume":"164","author":"NJ Haradhvala","year":"2016","unstructured":"Haradhvala, N. J. et al. Mutational strand asymmetries in cancer genomes reveal mechanisms of DNA damage and repair. Cell 164, 538\u2013549 (2016).","journal-title":"Cell"},{"key":"1670_CR23","doi-asserted-by":"publisher","first-page":"197ra101","DOI":"10.1126\/scitranslmed.3006086","volume":"5","author":"SL Poon","year":"2013","unstructured":"Poon, S. L. et al. Genome-wide mutational signatures of aristolochic acid and its application as a screening tool. Sci. Transl. Med. 5, 197ra101 (2013).","journal-title":"Sci. Transl. Med."},{"key":"1670_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6135","volume":"5","author":"G Scelo","year":"2014","unstructured":"Scelo, G. et al. Variation in genomic landscape of clear cell renal cell carcinoma across Europe. Nat. Commun. 5, 5135 (2014).","journal-title":"Nat. Commun."},{"key":"1670_CR25","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.fct.2018.11.047","volume":"124","author":"BR Rushing","year":"2019","unstructured":"Rushing, B. R. & Selim, M. I. Aflatoxin B1: a review on metabolism, toxicity, occurrence in food, occupational exposure, and detoxification methods. Food Chem. Toxicol. 124, 81\u2013100 (2019).","journal-title":"Food Chem. Toxicol."},{"key":"1670_CR26","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1126\/science.aau3879","volume":"362","author":"I Martincorena","year":"2018","unstructured":"Martincorena, I. et al. Somatic mutant clones colonize the human esophagus with age. Science 362, 911\u2013917 (2018).","journal-title":"Science"},{"key":"1670_CR27","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/s41586-018-0811-x","volume":"565","author":"A Yokoyama","year":"2019","unstructured":"Yokoyama, A. et al. Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature 565, 312\u2013317 (2019).","journal-title":"Nature"},{"key":"1670_CR28","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1002\/hep.27372","volume":"60","author":"JC Nault","year":"2014","unstructured":"Nault, J. C. et al. Telomerase reverse transcriptase promoter mutation is an early somatic genetic alteration in the transformation of premalignant nodules in hepatocellular carcinoma on cirrhosis. Hepatology 60, 1983\u20131992 (2014).","journal-title":"Hepatology"},{"key":"1670_CR29","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1007\/s00535-019-01555-z","volume":"54","author":"SK Kim","year":"2019","unstructured":"Kim, S. K. et al. Comprehensive analysis of genetic aberrations linked to tumorigenesis in regenerative nodules of liver cirrhosis. J. Gastroenterol. 54, 628\u2013640 (2019).","journal-title":"J. Gastroenterol."},{"key":"1670_CR30","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1016\/j.cell.2019.03.026","volume":"177","author":"M Zhu","year":"2019","unstructured":"Zhu, M. et al. Somatic mutations increase hepatic clonal fitness and regeneration in chronic liver disease. Cell 177, 608\u2013621 (2019).","journal-title":"Cell"},{"key":"1670_CR31","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1002\/hep.20701","volume":"41","author":"DE Kleiner","year":"2005","unstructured":"Kleiner, D. E. et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41, 1313\u20131321 (2005).","journal-title":"Hepatology"},{"key":"1670_CR32","doi-asserted-by":"publisher","unstructured":"Lee-Six, H. et al. The landscape of somatic mutation in normal colorectal epithelial cells. Nature\n                           https:\/\/doi.org\/10.1038\/s41586-019-1672-7 (2019).","DOI":"10.1038\/s41586-019-1672-7"},{"key":"1670_CR33","doi-asserted-by":"publisher","first-page":"15.10.1","DOI":"10.1002\/cpbi.20","volume":"56","author":"D Jones","year":"2016","unstructured":"Jones, D. et al. cgpCaVEManWrapper: Simple execution of CaVEMan in order to detect somatic single nucleotide variants in NGS data. Curr. Protoc. Bioinformatics 56, 15.10.1\u201315.10.18 (2016).","journal-title":"Curr. Protoc. Bioinformatics"},{"key":"1670_CR34","doi-asserted-by":"crossref","first-page":"15.8.1","DOI":"10.1002\/0471250953.bi1508s52","volume":"52","author":"A Menzies","year":"2015","unstructured":"Menzies, A. et al. VAGrENT: Variation Annotation Generator. Curr. Protoc. Bioinformatics 52, 15.8.1\u201315.8.11 (2015).","journal-title":"Curr. Protoc. Bioinformatics"},{"key":"1670_CR35","unstructured":"Dahl, D. B. An Improved Merge-Split Sampler for Conjugate Dirichlet Process Mixture Models. Technical Report No. 1086 (Univ. Wisconsin\u2013Madison, 2003)."},{"key":"1670_CR36","doi-asserted-by":"publisher","unstructured":"Papastamoulis, P. label.switching: An R package for dealing with the label switching problem in MCMC outputs. J. Stat. Softw. 69, https:\/\/doi.org\/10.18637\/jss.v069.c01 (2016).","DOI":"10.18637\/jss.v069.c01"},{"key":"1670_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7120","volume":"6","author":"A Fujimoto","year":"2015","unstructured":"Fujimoto, A. et al. Whole-genome mutational landscape of liver cancers displaying biliary phenotype reveals hepatitis impact and molecular diversity. Nat. Commun. 6, 6120 (2015).","journal-title":"Nat. Commun."},{"key":"1670_CR38","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1002\/hep.26540","volume":"58","author":"SP Cleary","year":"2013","unstructured":"Cleary, S. P. et al. Identification of driver genes in hepatocellular carcinoma by exome sequencing. Hepatology 58, 1693\u20131702 (2013).","journal-title":"Hepatology"},{"key":"1670_CR39","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1002\/hep.27198","volume":"60","author":"S-M Ahn","year":"2014","unstructured":"Ahn, S.-M. et al. Genomic portrait of resectable hepatocellular carcinomas: implications of RB1 and FGF19 aberrations for patient stratification. Hepatology 60, 1972\u20131982 (2014).","journal-title":"Hepatology"},{"key":"1670_CR40","doi-asserted-by":"crossref","first-page":"15.7.1","DOI":"10.1002\/0471250953.bi1507s52","volume":"52","author":"KM Raine","year":"2015","unstructured":"Raine, K. M. et al. cgpPindel: Identifying somatically acquired insertion and deletion events from paired end sequencing. Curr. Protoc. Bioinformatics 52, 15.7.1\u201315.7.12 (2015).","journal-title":"Curr. Protoc. Bioinformatics"},{"key":"1670_CR41","doi-asserted-by":"publisher","first-page":"15.9.1","DOI":"10.1002\/cpbi.17","volume":"56","author":"KM Raine","year":"2016","unstructured":"Raine, K. M. et al. ascatNgs: Identifying somatically acquired copy-number alterations from whole-genome sequencing data. Curr. Protoc. Bioinformatics 56, 15.9.1\u201315.9.17 (2016).","journal-title":"Curr. Protoc. Bioinformatics"},{"key":"1670_CR42","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1038\/ng.128","volume":"40","author":"PJ Campbell","year":"2008","unstructured":"Campbell, P. J. et al. Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing. Nat. Genet. 40, 722\u2013729 (2008).","journal-title":"Nat. Genet."},{"key":"1670_CR43","unstructured":"Alexandrov, L. et al. The repertoire of mutational signatures in human cancer. Preprint at https:\/\/www.biorxiv.org\/content\/10.1101\/322859v2 (2019)."},{"key":"1670_CR44","doi-asserted-by":"publisher","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":"1670_CR45","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1038\/nprot.2009.97","volume":"4","author":"S Durinck","year":"2009","unstructured":"Durinck, S., Spellman, P. T., Birney, E. & Huber, W. Mapping identifiers for the integration of genomic datasets with the R\/Bioconductor package biomaRt. Nat. Protoc. 4, 1184\u20131191 (2009).","journal-title":"Nat. Protocols"},{"key":"1670_CR46","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/nature24277","volume":"550","author":"GTEx Consortium","year":"2017","unstructured":"GTEx Consortium. Genetic effects on gene expression across human tissues. Nature 550, 204\u2013213 (2017).","journal-title":"Nature"},{"key":"1670_CR47","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-018-0539-0","volume":"10","author":"F Blokzijl","year":"2018","unstructured":"Blokzijl, F., Janssen, R., van Boxtel, R. & Cuppen, E. MutationalPatterns: comprehensive genome-wide analysis of mutational processes. Genome Med. 10, 33 (2018).","journal-title":"Genome Med."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41586-019-1670-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-019-1670-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-019-1670-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T17:59:50Z","timestamp":1684605590000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-019-1670-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,23]]},"references-count":47,"journal-issue":{"issue":"7779","published-print":{"date-parts":[[2019,10,24]]}},"alternative-id":["1670"],"URL":"https:\/\/doi.org\/10.1038\/s41586-019-1670-9","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,23]]},"assertion":[{"value":"17 November 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 October 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}