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dc.contributor.authorNg, A. W. T.
dc.contributor.authorContino, G.
dc.contributor.authorKillcoyne, S.
dc.contributor.authorDevonshire, G.
dc.contributor.authorHsu, R.
dc.contributor.authorAbbas, S.
dc.contributor.authorSu, J.
dc.contributor.authorRedmond, A. M.
dc.contributor.authorWeaver, Jamie M
dc.contributor.authorEldridge, M. D.
dc.contributor.authorTavaré, S.
dc.contributor.authorEdwards, P. A. W.
dc.contributor.authorFitzgerald, R. C.
dc.date.accessioned2022-05-26T08:35:12Z
dc.date.available2022-05-26T08:35:12Z
dc.date.issued2022en
dc.identifier.citationNg AWT, Contino G, Killcoyne S, Devonshire G, Hsu R, Abbas S, et al. Rearrangement processes and structural variations show evidence of selection in oesophageal adenocarcinomas. Vol. 5, Communications Biology. Springer Science and Business Media LLC; 2022.en
dc.identifier.pmid35396535en
dc.identifier.doi10.1038/s42003-022-03238-7en
dc.identifier.urihttp://hdl.handle.net/10541/625271
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.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1038/s42003-022-03238-7en
dc.titleRearrangement processes and structural variations show evidence of selection in oesophageal adenocarcinomasen
dc.typeArticleen
dc.contributor.departmentMedical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridgeen
dc.identifier.journalCommunications Biologyen
dc.description.noteen]
refterms.dateFOA2022-06-29T09:19:08Z


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