Show simple item record

dc.contributor.authorNones, K
dc.contributor.authorWaddell, N
dc.contributor.authorWayte, N
dc.contributor.authorPatch, A-M
dc.contributor.authorBailey, P
dc.contributor.authorNewell, F
dc.contributor.authorHolmes, O
dc.contributor.authorFink, JL
dc.contributor.authorQuinn, MCJ
dc.contributor.authorTang, YH
dc.contributor.authorLampe, G
dc.contributor.authorQuek, K
dc.contributor.authorLoffler, KA
dc.contributor.authorManning, S
dc.contributor.authorIdrisoglu, S
dc.contributor.authorMiller, D
dc.contributor.authorXu, Q
dc.contributor.authorWaddell, N
dc.contributor.authorWilson, PJ
dc.contributor.authorBruxner, TJC
dc.contributor.authorChrist, AN
dc.contributor.authorHarliwong, I
dc.contributor.authorNourse, C
dc.contributor.authorNourbakhsh, E
dc.contributor.authorAnderson, M
dc.contributor.authorKazakoff, S
dc.contributor.authorLeonard, C
dc.contributor.authorWood, S
dc.contributor.authorSimpson, PT
dc.contributor.authorReid, LE
dc.contributor.authorKrause, L
dc.contributor.authorHussey, DJ
dc.contributor.authorWatson, DI
dc.contributor.authorLord, RV
dc.contributor.authorNancarrow, D
dc.contributor.authorPhillips, WA
dc.contributor.authorGotley, D
dc.contributor.authorSmithers, BM
dc.contributor.authorWhiteman, DC
dc.contributor.authorHayward, NK
dc.contributor.authorCampbell, PJ
dc.contributor.authorPearson, JV
dc.contributor.authorGrimmond, SM
dc.contributor.authorBarbour, AP
dc.date.accessioned2021-02-05T00:43:46Z
dc.date.available2021-02-05T00:43:46Z
dc.date.issued2014-10-01
dc.identifier.citationNones, K., Waddell, N., Wayte, N., Patch, A. -M., Bailey, P., Newell, F., Holmes, O., Fink, J. L., Quinn, M. C. J., Tang, Y. H., Lampe, G., Quek, K., Loffler, K. A., Manning, S., Idrisoglu, S., Miller, D., Xu, Q., Waddell, N., Wilson, P. J. ,... Barbour, A. P. (2014). Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. NATURE COMMUNICATIONS, 5 (1), https://doi.org/10.1038/ncomms6224.
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11343/260126
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.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.titleGenomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis
dc.typeJournal Article
dc.identifier.doi10.1038/ncomms6224
melbourne.affiliation.departmentCentre for Cancer Research
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleNature Communications
melbourne.source.volume5
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1033243
melbourne.contributor.authorGrimmond, Sean
melbourne.contributor.authorPhillips, Wayne
dc.identifier.eissn2041-1723
melbourne.accessrightsOpen Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record