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dc.contributor.authorNones, Katia
dc.contributor.authorWaddell, Nicola
dc.contributor.authorWayte, Nicci
dc.contributor.authorPatch, Ann-Marie
dc.contributor.authorBailey, Peter
dc.contributor.authorNewell, Felicity
dc.contributor.authorHolmes, Oliver
dc.contributor.authorFink, J. Lynn
dc.contributor.authorQuinn, Michael C.J.
dc.contributor.authorTang, Yue Hang
dc.contributor.authorLampe, Guy
dc.contributor.authorQuek, Kelly
dc.contributor.authorLoffler, Kelly A
dc.contributor.authorManning, Suzanne
dc.contributor.authorIdrisoglu, Senel
dc.contributor.authorMiller, David
dc.contributor.authorXu, Qinying
dc.contributor.authorWaddell, Nick
dc.contributor.authorWilson, Peter J
dc.contributor.authorBruxner, Timothy J C
dc.contributor.authorChrist, Angelika N
dc.contributor.authorHarliwong, Ivon
dc.contributor.authorNourse, Craig
dc.contributor.authorNourbakhsh, Ehsan
dc.contributor.authorAnderson, Matthew F
dc.contributor.authorKazakoff, Stephen H
dc.contributor.authorLeonard, Conrad
dc.contributor.authorWood, Scott
dc.contributor.authorSimpson, Peter
dc.contributor.authorReid, Lynne E
dc.contributor.authorKrause, Lutz
dc.contributor.authorHussey, Damian James
dc.contributor.authorWatson, David Ian
dc.contributor.authorLord, Reginald V
dc.contributor.authorNancarrow, Derek J
dc.contributor.authorPhillips, Wayne A
dc.contributor.authorGotley, David C
dc.contributor.authorSmithers, B Mark
dc.contributor.authorWhiteman, David C
dc.contributor.authorHayward, Nicholas K
dc.contributor.authorCampbell, Peter J
dc.contributor.authorPearson, John V
dc.contributor.authorGrimmond, Sean M
dc.contributor.authorBarbour, Andrew P
dc.date.accessioned2015-02-23T00:09:29Z
dc.date.available2015-02-23T00:09:29Z
dc.date.issued2014
dc.identifier.citationNones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderson M, Kazakoff S, Leonard C, Wood S, Simpson PT, Reid LE, Krause L, Hussey DJ, Watson DI, Lord RV, Nancarrow D, Phillips WA, Gotley D, Smithers BM, Whiteman DC, Hayward NK, Campbell PJ, Pearson JV, Grimmond SM, Barbour AP. Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nature Communications. 2014 Oct 29;5:5224en
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/2328/35244
dc.descriptionThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en
dc.description.abstractOesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC.en
dc.language.isoen
dc.publisherNature Publishing Groupen
dc.relationhttp://purl.org/au-research/grants/NHMRC/1021403en
dc.rightsCopyright © 2014 Macmillan Publishers Limited. All rights reserved.en
dc.subjectChromosome breakageen
dc.subjectEsophageal neoplasmsen
dc.subjectGeneticsen
dc.titleGenomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesisen
dc.typeArticleen
dc.relation.grantnumberNHMRC/1021403en
dc.identifier.doihttps://doi.org/10.1038/ncomms6224en
dc.rights.holderMacmillan Publishers Limiteden
local.contributor.authorOrcidLookupHussey, Damian James: https://orcid.org/0000-0002-6121-6740en_US
local.contributor.authorOrcidLookupLoffler, Kelly A: https://orcid.org/0000-0003-3302-5995en_US
local.contributor.authorOrcidLookupWatson, David Ian: https://orcid.org/0000-0002-7683-2693en_US


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