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dc.contributor.authorDavidson, M
dc.contributor.authorBarber, LJ
dc.contributor.authorWoolston, A
dc.contributor.authorCafferkey, C
dc.contributor.authorMansukhani, S
dc.contributor.authorGriffiths, B
dc.contributor.authorMoorcraft, S-Y
dc.contributor.authorRana, I
dc.contributor.authorBegum, R
dc.contributor.authorAssiotis, I
dc.contributor.authorMatthews, N
dc.contributor.authorRao, S
dc.contributor.authorWatkins, D
dc.contributor.authorChau, I
dc.contributor.authorCunningham, D
dc.contributor.authorStarling, N
dc.contributor.authorGerlinger, M
dc.date.accessioned2019-06-05T09:53:44Z
dc.date.accessioned2019-06-05T10:07:43Z
dc.date.issued2019-05-27
dc.identifier.citationCancers, 2019, 11 (5)
dc.identifier.issn2072-6694
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3254
dc.identifier.eissn2072-6694en_US
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.
dc.formatElectronic
dc.languageeng
dc.language.isoeng
dc.relation.replaceshttps://repository.icr.ac.uk/handle/internal/3253
dc.relation.replacesinternal/3253
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleDetecting and Tracking Circulating Tumour DNA Copy Number Profiles during First Line Chemotherapy in Oesophagogastric Adenocarcinoma.
dc.typeJournal Article
dcterms.dateAccepted2019-05-23
rioxxterms.versionofrecord10.3390/cancers11050736
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-05-27en_US
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancers
pubs.issue5
pubs.notesNot known
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.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
pubs.volume11en_US
pubs.embargo.termsNot known
icr.researchteamGastrointestinal Cancers Clinical Trialsen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamTranslational Oncogenomicsen_US
atmire.cua.enabled
dc.contributor.icrauthorGriffiths, Beatriceen
dc.contributor.icrauthorMansukhani, Soniaen
dc.contributor.icrauthorBarber, Louiseen
dc.contributor.icrauthorCunningham, Daviden
dc.contributor.icrauthorChau, Ianen
dc.contributor.icrauthorStarling, Naureenen
dc.contributor.icrauthorGerlinger, Marcoen
dc.contributor.icrauthorWoolston, Andrewen


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