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dc.contributor.authorNg, Alvin Wei Tian
dc.contributor.authorContino, Gianmarco
dc.contributor.authorKillcoyne, Sarah
dc.contributor.authorDevonshire, Ginny
dc.contributor.authorHsu, Ray
dc.contributor.authorAbbas, Sujath
dc.contributor.authorSu, Jing
dc.contributor.authorRedmond, Aisling M
dc.contributor.authorWeaver, Jamie MJ
dc.contributor.authorEldridge, Matthew
dc.contributor.authorTavaré, Simon
dc.contributor.authorOesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium
dc.contributor.authorEdwards, Paul AW
dc.contributor.authorFitzgerald, Rebecca
dc.date.accessioned2022-04-08T15:00:24Z
dc.date.available2022-04-08T15:00:24Z
dc.date.issued2022-04-08
dc.date.submitted2021-09-07
dc.identifier.issn2399-3642
dc.identifier.others42003-022-03238-7
dc.identifier.other3238
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/335914
dc.description.abstractOesophageal adenocarcinoma (OAC) provides an ideal case study to characterize large-scale rearrangements. Using whole genome short-read sequencing of 383 cases, for which 214 had matched whole transcriptomes, we observed structural variations (SV) with a predominance of deletions, tandem duplications and inter-chromosome junctions that could be identified as LINE-1 mobile element (ME) insertions. Complex clusters of rearrangements resembling breakage-fusion-bridge cycles or extrachromosomal circular DNA accounted for 22% of complex SVs affecting known oncogenes. Counting SV events affecting known driver genes substantially increased the recurrence rates of these drivers. After excluding fragile sites, we identified 51 candidate new drivers in genomic regions disrupted by SVs, including ETV5, KAT6B and CLTC. RUNX1 was the most recurrently altered gene (24%), with many deletions inactivating the RUNT domain but preserved the reading frame, suggesting an altered protein product. These findings underscore the importance of identification of SV events in OAC with implications for targeted therapies.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/67/1504/1477
dc.subject/631/67/69
dc.subject/631/67/395
dc.subject/631/67/1244
dc.subject/45
dc.subject/45/23
dc.subject/45/22
dc.subjectarticle
dc.titleRearrangement processes and structural variations show evidence of selection in oesophageal adenocarcinomas.
dc.typeArticle
dc.date.updated2022-04-08T15:00:23Z
prism.issueIdentifier1
prism.publicationNameCommun Biol
prism.volume5
dc.identifier.doi10.17863/CAM.83347
dcterms.dateAccepted2022-02-25
rioxxterms.versionofrecord10.1038/s42003-022-03238-7
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidNg, Alvin Wei Tian [0000-0003-4672-0815]
dc.contributor.orcidDevonshire, Ginny [0000-0002-1408-8176]
dc.contributor.orcidEldridge, Matthew [0000-0002-5799-8911]
dc.contributor.orcidEdwards, Paul AW [0000-0002-4789-3374]
dc.contributor.orcidFitzgerald, Rebecca [0000-0002-3434-3568]
dc.identifier.eissn2399-3642
pubs.funder-project-idNational Institute for Health Research (NIHRDH-IS-BRC-1215-20014)
cam.issuedOnline2022-04-08


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