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dc.contributor.authorNewell, Felicityen_US
dc.contributor.authorPatel, Kalpanaen_US
dc.contributor.authorGartside, Michaelen_US
dc.contributor.authorKrause, Lutzen_US
dc.contributor.authorBrosda, Sandraen_US
dc.contributor.authorAoude, Lauren Gen_US
dc.contributor.authorLoffler, Kelly Aen_US
dc.contributor.authorBonazzi, Vanessa Fen_US
dc.contributor.authorPatch, Ann-Marieen_US
dc.contributor.authorKazakoff, Stephen Hen_US
dc.contributor.authorHolmes, Oliveren_US
dc.contributor.authorXu, Qinyingen_US
dc.contributor.authorWood, Scotten_US
dc.contributor.authorLeonard, Conraden_US
dc.contributor.authorLampe, Guyen_US
dc.contributor.authorLord, Reginald Ven_US
dc.contributor.authorWhiteman, David Cen_US
dc.contributor.authorPearson, John Ven_US
dc.contributor.authorNones, Katiaen_US
dc.contributor.authorWaddell, Nicolaen_US
dc.contributor.authorBarbour, Andrew Pen_US
dc.date.accessioned2019-02-20T05:31:13Z
dc.date.available2019-02-20T05:31:13Z
dc.date.issued2019-02-04
dc.identifier.citationNewell, F., Patel, K., Gartside, M., Krause, L., Brosda, S., Aoude, L. G., … Barbour, A. P. (2019). Complex structural rearrangements are present in high-grade dysplastic Barrett’s oesophagus samples. BMC Medical Genomics, 12(1). https://doi.org/10.1186/s12920-019-0476-9en_US
dc.identifier.issn1755-8794
dc.identifier.urihttps://doi.org/10.1186/s12920-019-0476-9
dc.identifier.urihttp://hdl.handle.net/2328/38987
dc.descriptionThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.en_US
dc.description.abstractAbstract Background Oesophageal adenocarcinoma (EAC) incidence is increasing and has a poor survival rate. Barrett’s oesophagus (BE) is a precursor condition that is associated with EAC and often occurs in conjunction with chronic gastro-oesophageal reflux, however many individuals diagnosed with BE never progress to cancer. An understanding of the genomic features of BE and EAC may help with the early identification of at-risk individuals. Methods In this study, we assessed the genomic features of 16 BE samples using whole-genome sequencing. These included non-dysplastic samples collected at two time-points from two BE patients who had not progressed to EAC over several years. Seven other non-dysplastic samples and five dysplastic BE samples with high-grade dysplasia were also examined. We compared the genome profiles of these 16 BE samples with 22 EAC samples. Results We observed that samples from the two non-progressor individuals had low numbers of somatic single nucleotide variants, indels and structural variation events compared to dysplastic and the remaining non-dysplastic BE. EAC had the highest level of somatic genomic variations. Mutational signature 17, which is common in EAC, was also present in non-dysplastic and dysplastic BE, but was not present in the non-progressors. Many dysplastic samples had mutations in genes previously reported in EAC, whereas only mutations in CDKN2A or in the fragile site genes appeared common in non-dysplastic samples. Rearrangement signatures were used to identify a signature associated with localised complex events such as chromothripsis and breakage fusion-bridge that are characteristic of EACs. Two dysplastic BE samples had a high contribution of this signature and contained evidence of localised rearrangements. Two other dysplastic samples also had regions of localised structural rearrangements. There was no evidence for complex events in non-dysplastic samples. Conclusions The presence of complex localised rearrangements in dysplastic samples indicates a need for further investigations into the role such events play in the progression from BE to EAC.en_US
dc.language.isoenen_US
dc.publisherBioMed Centralen_US
dc.relationhttp://purl.org/au-research/grants/nhmrc/1021403en_US
dc.relationhttp://purl.org/au-research/grants/nhmrc/1040947en_US
dc.relationhttp://purl.org/au-research/grants/nhmrc/1112113en_US
dc.relationhttp://purl.org/au-research/grants/nhmrc/1139071en_US
dc.relationhttp://purl.org/au-research/grants/nhmrc/1109048en_US
dc.relationhttp://purl.org/au-research/grants/nhmrc/1058522en_US
dc.rights© The Author(s). 2019en_US
dc.subjectOesophageal adenocarcinomaen_US
dc.subjectBarrett’s oesophagusen_US
dc.subjectChromothripsisen_US
dc.subjectBreakage-fusion bridgeen_US
dc.subjectWhole-genome sequencingen_US
dc.titleComplex structural rearrangements are present in high-grade dysplastic Barrett’s oesophagus samplesen_US
dc.typeArticleen_US
dc.relation.grantnumberNHMRC/1021403en_US
dc.relation.grantnumberNHMRC/1040947en_US
dc.relation.grantnumberNHMRC/1112113en_US
dc.relation.grantnumberNHMRC/1139071en_US
dc.relation.grantnumberNHMRC/1109048en_US
dc.relation.grantnumberNHMRC/1058522en_US
dc.identifier.doihttps://doi.org/10.1186/s12920-019-0476-9en_US
dc.date.updated2019-02-20T04:54:19Z
dc.language.rfc3066en
dc.rights.holderThe Author(s).en_US
local.contributor.authorOrcidLookupLoffler, Kelly A: https://orcid.org/0000-0003-3302-5995en_US
local.contributor.authorOrcidLookupNewell, Felicity: https://orcid.org/0000-0003-0469-2705en_US


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