Show simple item record

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 D
dc.contributor.authorTavaré, Simon
dc.contributor.authorOesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium
dc.contributor.authorEdwards, Paul AW
dc.contributor.authorFitzgerald, Rebecca C
dc.date.accessioned2022-05-10T01:01:47Z
dc.date.available2022-05-10T01:01:47Z
dc.date.issued2022-04-08
dc.identifier.issn2399-3642
dc.identifier.other35396535
dc.identifier.otherPMC8993906
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336962
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.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101719179
dc.sourceessn: 2399-3642
dc.subjectHumans
dc.subjectAdenocarcinoma
dc.subjectEsophageal Neoplasms
dc.subjectGenome, Human
dc.subjectHistone Acetyltransferases
dc.subjectWhole Genome Sequencing
dc.titleRearrangement processes and structural variations show evidence of selection in oesophageal adenocarcinomas.
dc.typeArticle
dc.date.updated2022-05-10T01:01:42Z
prism.issueIdentifier1
prism.publicationNameCommun Biol
prism.volume5
dc.identifier.doi10.17863/CAM.84385
dcterms.dateAccepted2022-02-25
rioxxterms.versionofrecord10.1038/s42003-022-03238-7
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://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 D [0000-0002-5799-8911]
dc.contributor.orcidEdwards, Paul AW [0000-0002-4789-3374]
dc.contributor.orcidFitzgerald, Rebecca C [0000-0002-3434-3568]
dc.identifier.eissn2399-3642
pubs.funder-project-idNational Institute for Health Research (IS-BRC-1215-20014)
cam.issuedOnline2022-04-08


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International