{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gimeno-Valiente F"],"funding":["Regional Government of Valencia | Conselleria d'Educació, Investigació, Cultura i Esport (Conselleria d'Educació, Investigació, Cultura i Esport de la Generalitat Valenciana)","Wellcome Trust"],"pagination":["2226-2237"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12425823"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["57(9)"],"pubmed_abstract":["Aberrant DNA methylation has been described in nearly all human cancers, yet its interplay with genomic alterations during tumor evolution is poorly understood. To explore this, we performed reduced representation bisulfite sequencing on 217 tumor and matched normal regions from 59 patients with non-small cell lung cancer from the TRACERx study to deconvolve tumor methylation. We developed two metrics for integrative evolutionary analysis with DNA and RNA sequencing data. Intratumoral methylation distance quantifies intratumor DNA methylation heterogeneity. M<sub>R</sub>/M<sub>N</sub> classifies genes based on the rate of hypermethylation at regulatory (M<sub>R</sub>) versus nonregulatory (M<sub>N</sub>) CpGs to identify driver genes exhibiting recurrent functional hypermethylation. We ide"],"journal":["Nature genetics"],"pubmed_title":["DNA methylation cooperates with genomic alterations during non-small cell lung cancer evolution."],"pmcid":["PMC12425823"],"funding_grant_id":["APOSTD/2021/168","CC2041","CC2008","WT209199/Z/17/Z","211179/Z/18/Z","218274/Z/19/Z"],"pubmed_authors":["Litovchenko M","Osman A","Bailey C","Stavrou G","Atkin A","Stephens RCM","Fraioli F","Stone RK","Thakrar RM","Pilotti C","Biswas D","Sivakumar M","McGranahan N","Zaidi R","Prymas P","Thol K","Alzetani A","Brown KD","Yuan Y","Hackshaw A","De Sousa P","Chavan H","Wilson GA","Rowan A","Asif M","Chaturvedi A","Gronroos E","Langman G","Russell P","Fennell DA","Naito Y","Martinez-Ruiz C","Forster MD","Malima M","Kerr KM","Novasio J","Khiroya R","Shackleford H","Summers Y","Steif J","Benafif S","Watkins TBK","Nicod J","Veeriah S","Lee SM","Grapa A","Mussa B","Bishop P","Kaplar Z","Dwornik A","Usaite I","Bola SK","Le Quesne J","Djearaman M","Black JRM","Paiva-Correia A","Hill W","Bajaj A","Patrini D","Spanswick V","Pich O","Colliver E","Tanic M","Kostoulas N","Tugwood J","Carter M","Dhami P","AbdulJabbar K","Blyth KG","Bakir MA","Chen K","Demeulemeester J","Proli C","Fernandes N","Collins-Fekete CA","Rathinam S","Taylor MN","Escudero M","Gilbert K","Pawlik P","Janes SM","Begum S","Szallasi Z","Swanton C","Sangha M","Chuter D","Bhayani H","Boeing S","Rammohan K","Lindsay CR","Liu X","Lu WT","Liu WK","Moore DA","Monk F","Khalil M","Patel AJ","Naceur-Lombardelli C","Toncheva A","Jordan S","Scott R","Shackcloth MJ","Rane JK","Koh K","Angelova M","Chee S","Vaikkinen H","Kassiotis G","Hobson P","Kidd A","Grigoriadis K","Boleti E","Oliveira P","Zhang Z","Lim E","Lai S","Scotland M","Kaufmann TL","Dulloo S","Shah M","Papadatos-Pastos D","Bandula S","Shah P","Zhang H","Wilson J","Whiteley J","Crosbie P","Bilancia R","Quezada SA","Leek A","Leslie R","Goldman J","Sahai E","Totton N","Weeden CE","Royle G","Lucas O","Bhakhri K","Pisciella MC","Ahmed A","Selvaraju K","Gorman P","Tufail M","Waplington S","Beck S","Richardson S","Wong YNS","Fontaine E","Hacker AM","Castignani C","Kanu N","Murphy C","Kaniu D","Cheyne H","Saghafinia S","Choudhary J","Rice A","Danson S","Bunkum A","Dive C","Schwarz RF","MacKenzie M","Jones TP","Harries S","Holding JW","Reading JL","Keene E","Hewish M","Dietzen M","Deniz O","Hessey S","Dick C","Lee C","Zagorulya M","Hartley JA","Georg P","Thomas M","Hirst M","Pearce DR","Navani N","Matharu G","Veiga C","Booth S","Lester JF","Nicholson AG","Kirk A","Price G","Noorani I","Kittel J","Buderi SI","Karamani A","Richard C","Ashford P","Falzon M","Wilson C","Birkbak NJ","Ung SKA","Cave J","Nakas A","Karagianni D","Leung MM","Zaccaria S","Barbe V","Sodha-Ramdeen A","Karasaki T","Mastrokalos GT","Patruno L","Ahmad T","Aerts HJWL","Middleton G","Marafioti T","Feber A","Enfield KSS","Ensell L","Hodgkinson JD","Wu Y","Shaw JA","Puttick C","Blackhall FH","Lowe HL","Gimeno-Valiente F","Magala M","Procter AJ","Hynds RE","Jamal-Hanjani M","Haase K","Vendramin R","Krebs MG","Gamble S","Peggs KS","Bentham R","Ramsden Z","Raubenheimer H","Chain B","Huebner A","Rosenthal R","Van Loo P","French J","Naidu B","Hiley C","Ward S","Chervova O","Walker A","Larose Cadieux E","Joshi V","Thakkar K","Denner T","Lawrence D","Frankell AM","Boyles R","Vanloo S","Pan X","TRACERx Consortium","Robinson L","Hoogenboom EM","Ambrose L","Devaraj A","Mensah NE","Diossy M","Joseph L","Granato F","Smith S","Marinelli D","Borg E","Salgado R","Nye E","Lim EL","Cruickshank T","Nair A"],"additional_accession":[]},"is_claimable":false,"name":"DNA methylation cooperates with genomic alterations during non-small cell lung cancer evolution.","description":"Aberrant DNA methylation has been described in nearly all human cancers, yet its interplay with genomic alterations during tumor evolution is poorly understood. To explore this, we performed reduced representation bisulfite sequencing on 217 tumor and matched normal regions from 59 patients with non-small cell lung cancer from the TRACERx study to deconvolve tumor methylation. We developed two metrics for integrative evolutionary analysis with DNA and RNA sequencing data. Intratumoral methylation distance quantifies intratumor DNA methylation heterogeneity. M<sub>R</sub>/M<sub>N</sub> classifies genes based on the rate of hypermethylation at regulatory (M<sub>R</sub>) versus nonregulatory (M<sub>N</sub>) CpGs to identify driver genes exhibiting recurrent functional hypermethylation. We ide","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-03T02:49:45.708Z","creation":"2026-04-23T03:12:27.867Z"},"accession":"S-EPMC12425823","cross_references":{"pubmed":["40931149"],"doi":["10.1038/s41588-025-02307-x"]}}