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dc.contributor.authorDavidson, Men_US
dc.contributor.authorBarber, LJen_US
dc.contributor.authorWoolston, Aen_US
dc.contributor.authorCafferkey, Cen_US
dc.contributor.authorMansukhani, Sen_US
dc.contributor.authorGriffiths, Ben_US
dc.contributor.authorMoorcraft, S-Yen_US
dc.contributor.authorRana, Ien_US
dc.contributor.authorBegum, Ren_US
dc.contributor.authorAssiotis, Ien_US
dc.contributor.authorMatthews, Nen_US
dc.contributor.authorRao, Sen_US
dc.contributor.authorWatkins, Den_US
dc.contributor.authorChau, Ien_US
dc.contributor.authorCunningham, Den_US
dc.contributor.authorStarling, Nen_US
dc.contributor.authorGerlinger, Men_US
dc.coverage.spatialSwitzerlanden_US
dc.date.accessioned2019-06-05T09:53:44Z
dc.date.accessioned2019-06-05T10:07:43Z
dc.date.issued2019-05-27en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/31137920en_US
dc.identifiercancers11050736en_US
dc.identifier.citationCancers (Basel), 2019, 11 (5)en_US
dc.identifier.issn2072-6694en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3254
dc.identifier.doi10.3390/cancers11050736en_US
dc.description.abstractDNA somatic copy number aberrations (SCNAs) are key drivers in oesophagogastric adenocarcinoma (OGA). Whether minimally invasive SCNA analysis of circulating tumour (ct)DNA can predict treatment outcomes and reveal how SCNAs evolve during chemotherapy is unknown. We investigated this by low-coverage whole genome sequencing (lcWGS) of ctDNA from 30 patients with advanced OGA prior to first-line chemotherapy and on progression. SCNA profiles were detectable pretreatment in 23/30 (76.7%) patients. The presence of liver metastases, primary tumour in situ, or of oesophageal or junctional tumour location predicted for a high ctDNA fraction. A low ctDNA concentration associated with significantly longer overall survival. Neither chromosomal instability metrics nor ploidy correlated with chemotherapy outcome. Chromosome 2q and 8p gains before treatment were associated with chemotherapy responses. lcWGS identified all amplifications found by prior targeted tumour tissue sequencing in cases with detectable ctDNA as well as finding additional changes. SCNA profiles changed during chemotherapy, indicating that cancer cell populations evolved during treatment; however, no recurrent SCNA changes were acquired at progression. Tracking the evolution of OGA cancer cell populations in ctDNA is feasible during chemotherapy. The observation of genetic evolution warrants investigation in larger series and with higher resolution techniques to reveal potential genetic predictors of response and drivers of chemotherapy resistance. The presence of liver metastasis is a potential biomarker for the selection of patients with high ctDNA content for such studies.en_US
dc.languageengen_US
dc.language.isoengen_US
dc.relation.replaceshttps://repository.icr.ac.uk/handle/internal/3253
dc.relation.replacesinternal/3253
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectcirculating tumour DNAen_US
dc.subjectliquid biopsyen_US
dc.subjectoesophagogastric adenocarcinomaen_US
dc.subjectsomatic copy number aberrationen_US
dc.titleDetecting and Tracking Circulating Tumour DNA Copy Number Profiles during First Line Chemotherapy in Oesophagogastric Adenocarcinoma.en_US
dc.typeJournal Article
dcterms.dateAccepted2019-05-23en_US
rioxxterms.versionofrecord10.3390/cancers11050736en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2019-05-27en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfCancers (Basel)en_US
pubs.issue5en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Gastrointestinal Cancers Clinical Trials/Gastrointestinal Cancers Clinical Trials (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Oncogenomics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished onlineen_US
pubs.volume11en_US
pubs.embargo.termsNot knownen_US
icr.researchteamGastrointestinal Cancers Clinical Trialsen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamTranslational Oncogenomicsen_US
atmire.cua.enabled
dc.contributor.icrauthorBarber, Louiseen_US
dc.contributor.icrauthorCunningham, Daviden_US
dc.contributor.icrauthorChau, Ianen_US
dc.contributor.icrauthorStarling, Naureenen_US
dc.contributor.icrauthorGerlinger, Marcoen_US
dc.contributor.icrauthorGriffiths, Beatriceen_US
dc.contributor.icrauthorMansukhani, Soniaen_US
dc.contributor.icrauthorWoolston, Andrewen_US


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