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dc.contributor.authorTexeira, Vitor H.
dc.contributor.authorPipinikas, Chrisodoulos P.
dc.contributor.authorPennycuick, Adam
dc.contributor.authorLee-Six, Henry
dc.contributor.authorChandrasekharan, Deepak
dc.contributor.authorBeane, Jennifer
dc.contributor.authorMorris, Tiffany J.
dc.contributor.authorKarpathakis, Anna
dc.contributor.authorFeber, Andrew
dc.contributor.authorBreeze, Charles E.
dc.contributor.authorNtolios, Paschalis
dc.contributor.authorHynds, Robert E.
dc.contributor.authorFalzon, Mary
dc.contributor.authorCapitanio, Arrigo
dc.contributor.authorCarroll, Bernadette
dc.contributor.authorDurrenberger, Pascal F.
dc.contributor.authorHardavella, Georgia
dc.contributor.authorBrown, James M.
dc.contributor.authorLynch, Andy G.
dc.contributor.authorFarmery, Henry
dc.contributor.authorPaul, Dirk S.
dc.contributor.authorChambers, Rachel C.
dc.contributor.authorMcGranahan, Nicholas
dc.contributor.authorNavani, Neal
dc.contributor.authorThakrar, Ricky M.
dc.contributor.authorSwanton, Charles
dc.contributor.authorBeck, Stephan
dc.contributor.authorGeorge, Philip Jeremy
dc.contributor.authorSpira, Avrum
dc.contributor.authorCampbell, Peter J.
dc.contributor.authorThirwell, Christina
dc.contributor.authorJanes, Sam M.
dc.identifier.citationTexeira , V H , Pipinikas , C P , Pennycuick , A , Lee-Six , H , Chandrasekharan , D , Beane , J , Morris , T J , Karpathakis , A , Feber , A , Breeze , C E , Ntolios , P , Hynds , R E , Falzon , M , Capitanio , A , Carroll , B , Durrenberger , P F , Hardavella , G , Brown , J M , Lynch , A G , Farmery , H , Paul , D S , Chambers , R C , McGranahan , N , Navani , N , Thakrar , R M , Swanton , C , Beck , S , George , P J , Spira , A , Campbell , P J , Thirwell , C & Janes , S M 2019 , ' Deciphering the genomic, epigenomic and transcriptomic landscapes of pre-invasive lung cancer lesions ' , Nature Medicine , vol. 25 , pp. 517-525 .
dc.identifier.otherPURE: 257052328
dc.identifier.otherPURE UUID: 07412353-99af-4ac3-a9ff-e762e6e6a39c
dc.identifier.otherORCID: /0000-0002-7876-7338/work/53214537
dc.identifier.otherScopus: 85060343299
dc.identifier.otherWOS: 000460643100031
dc.description.abstractThe molecular alterations that occur in cells before cancer is manifest are largely uncharted. Lung carcinoma in situ (CIS) lesions are the pre-invasive precursor to squamous cell carcinoma. Although microscopically identical, their future is in equipoise, with half progressing to invasive cancer and half regressing or remaining static. The cellular basis of this clinical observation is unknown. Here, we profile the genomic, transcriptomic, and epigenomic landscape of CIS in a unique patient cohort with longitudinally monitored pre-invasive disease. Predictive modeling identifies which lesions will progress with remarkable accuracy. We identify progression-specific methylation changes on a background of widespread heterogeneity, alongside a strong chromosomal instability signature. We observed mutations and copy number changes characteristic of cancer and chart their emergence, offering a window into early carcinogenesis. We anticipate that this new understanding of cancer precursor biology will improve early detection, reduce overtreatment, and foster preventative therapies targeting early clonal events in lung cancer.
dc.relation.ispartofNature Medicineen
dc.rightsCopyright © 2019, the Author(s). This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at
dc.subjectQA Mathematicsen
dc.subjectQH426 Geneticsen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.titleDeciphering the genomic, epigenomic and transcriptomic landscapes of pre-invasive lung cancer lesionsen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews.Cellular Medicine Divisionen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Statisticsen
dc.contributor.institutionUniversity of St Andrews.Sir James Mackenzie Institute for Early Diagnosisen
dc.description.statusPeer revieweden

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