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dc.contributor.authorSclafani, F
dc.contributor.authorChau, I
dc.contributor.authorCunningham, D
dc.contributor.authorHahne, JC
dc.contributor.authorVlachogiannis, G
dc.contributor.authorEltahir, Z
dc.contributor.authorLampis, A
dc.contributor.authorBraconi, C
dc.contributor.authorKalaitzaki, E
dc.contributor.authorDe Castro, DG
dc.contributor.authorWotherspoon, A
dc.contributor.authorCapdevila, J
dc.contributor.authorGlimelius, B
dc.contributor.authorTarazona, N
dc.contributor.authorBegum, R
dc.contributor.authorLote, H
dc.contributor.authorHulkki Wilson, S
dc.contributor.authorMentrasti, G
dc.contributor.authorBrown, G
dc.contributor.authorTait, D
dc.contributor.authorOates, J
dc.contributor.authorValeri, N
dc.date.accessioned2018-06-05T08:15:06Z
dc.date.issued2018-01-23
dc.identifier.citationScientific reports, 2018, 8 (1), pp. 1445 - ?
dc.identifier.issn2045-2322
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1700
dc.identifier.eissn2045-2322
dc.identifier.doi10.1038/s41598-018-19212-5
dc.description.abstractThere are limited data on circulating, cell-free, tumour (ct)DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples of 97 LARC patients who were treated with CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX ± cetuximab in a randomised phase II trial. KRAS mutation in G12D, G12V or G13D was detected in the ctDNA of 43% and 35% of patients with tumours that were mutant and wild-type for these hotspot mutations, respectively, according to standard PCR-based analyses on tissue. The detection rate in the ctDNA of 10 patients with less common mutations was 50%. In 26 cases ctDNA analysis revealed KRAS mutations that were not previously found in tissue. Twenty-two of these (84.6%) were detected following repeat tissue testing by ddPCR. Overall, the ctDNA detection rate in the KRAS mutant population was 66%. Detection of KRAS mutation in ctDNA failed to predict prognosis or refine patient selection for cetuximab. While this study confirms the feasibility of ctDNA analysis in LARC and the high sensitivity of ddPCR, larger series are needed to better address the role of ctDNA as a prognostic or predictive tool in this setting.
dc.formatElectronic
dc.format.extent1445 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectRectal Neoplasms
dc.subjectOrganoplatinum Compounds
dc.subjectProto-Oncogene Proteins B-raf
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectPrognosis
dc.subjectTreatment Outcome
dc.subjectDigestive System Surgical Procedures
dc.subjectMutation
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectProto-Oncogene Proteins p21(ras)
dc.subjectChemoradiotherapy, Adjuvant
dc.subjectCapecitabine
dc.subjectCetuximab
dc.subjectCirculating Tumor DNA
dc.subjectOxaliplatin
dc.titleKRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer.
dc.typeJournal Article
dcterms.dateAccepted2017-12-27
rioxxterms.versionofrecord10.1038/s41598-018-19212-5
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-01-23
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfScientific reports
pubs.issue1
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
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/Evolutionary Genomics & Modelling
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
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/Evolutionary Genomics & Modelling
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume8
pubs.embargo.termsNot known
icr.researchteamSignal Transduction & Molecular Pharmacologyen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamEvolutionary Genomics & Modellingen_US
icr.researchteamGastrointestinal Cancer Biology and Genomicsen_US
dc.contributor.icrauthorHahne, Jensen
dc.contributor.icrauthorBraconi, Chiaraen
dc.contributor.icrauthorLampis, Andreaen
dc.contributor.icrauthorChau, Ianen
dc.contributor.icrauthorCunningham, Daviden
dc.contributor.icrauthorValeri, Nicolaen


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