Show simple item record

dc.contributor.authorDavidson, M
dc.contributor.authorAronson, LI
dc.contributor.authorHoward-Reeves, J
dc.contributor.authorBryant, H
dc.contributor.authorCutts, RJ
dc.contributor.authorHulkki-Wilson, S
dc.contributor.authorKouvelakis, K
dc.contributor.authorKalaitzaki, E
dc.contributor.authorWatkins, D
dc.contributor.authorStarling, N
dc.contributor.authorRao, S
dc.contributor.authorCardenosa, ML
dc.contributor.authorBegum, R
dc.contributor.authorRana, I
dc.contributor.authorLazaro-Alcausi, R
dc.contributor.authorTerlizzo, M
dc.contributor.authorWotherspoon, A
dc.contributor.authorBrown, G
dc.contributor.authorSwansbury, J
dc.contributor.authorLord, CJ
dc.contributor.authorCunningham, D
dc.contributor.authorChau, I
dc.contributor.authorChong, IY
dc.date.accessioned2020-09-30T10:49:28Z
dc.date.issued2019-11
dc.identifier.citationEuropean journal of cancer (Oxford, England : 1990), 2019, 122 pp. 12 - 21
dc.identifier.issn0959-8049
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4090
dc.identifier.eissn1879-0852
dc.identifier.doi10.1016/j.ejca.2019.09.003
dc.description.abstractIntroduction The MYC proto-oncogene is among the most commonly dysregulated genes in human cancers. We report screening data from the iMYC trial, an ongoing phase II study assessing ibrutinib monotherapy in advanced pretreated MYC- and/or HER2-amplified oesophagogastric cancer, representing the first attempt to prospectively identify MYC amplifications in this tumour type for the purposes of therapeutic targeting.Methods Screening utilising a fluorescent in situ hybridisation (FISH) assay for assessment of tumour MYC amplification has been instituted. An experimental digital droplet polymerase chain reaction (ddPCR) assay to assess MYC amplification in both tumour and circulating-tumour (ct)DNA has been developed and investigated.Results One hundred thirty-five archival tumour specimens have undergone successful FISH analysis with 23% displaying evidence of MYC amplification. Intertumour heterogeneity was observed, with the percentage of cancer cells harbouring MYC amplification ranging widely between samples (median 51%, range 11-94%). Intratumoural clonal diversity of MYC amplification was also observed, with a significant degree of variance in amplification ratios (Bartlett's test for equal variance p < 0.001), and an association between greater variance in MYC amplification and improved outcome with prior first-line chemotherapy. ddPCR was most accurate in quantifying MYC amplification in tumour-derived DNA from cases with a high proportion (>70%) of amplified cells within the tumour specimen but was not reliable in samples containing a low proportion of amplified cells or in ctDNA.Conclusions Our results illustrate the utility of FISH to assess MYC amplification prospectively for a biomarker-selected trial by providing reliable and reproducible results in real time, with a high degree of heterogeneity of MYC amplification observed. We show that ddPCR can potentially detect high-level MYC amplifications in tumour tissue.
dc.formatPrint-Electronic
dc.format.extent12 - 21
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectEsophageal Neoplasms
dc.subjectStomach Neoplasms
dc.subjectProto-Oncogene Proteins c-myc
dc.subjectIn Situ Hybridization, Fluorescence
dc.subjectProspective Studies
dc.subjectPolymerase Chain Reaction
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectEarly Detection of Cancer
dc.subjectBiomarkers, Tumor
dc.titleClonal diversity of MYC amplification evaluated by fluorescent in situ hybridisation and digital droplet polymerase chain reaction in oesophagogastric cancer: Results from a prospective clinical trial screening programme.
dc.typeJournal Article
dcterms.dateAccepted2019-09-03
rioxxterms.versionofrecord10.1016/j.ejca.2019.09.003
rioxxterms.licenseref.startdate2019-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEuropean journal of cancer (Oxford, England : 1990)
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/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
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/Ashworth Collaborators
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
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/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
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/Ashworth Collaborators
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume122
pubs.embargo.termsNot known
icr.researchteamGastrointestinal Cancers Clinical Trialsen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamAshworth Collaboratorsen_US
icr.researchteamGene Functionen_US
dc.contributor.icrauthorCunningham, Daviden
dc.contributor.icrauthorChau, Ianen
dc.contributor.icrauthorLord, Christopheren
dc.contributor.icrauthorStarling, Naureenen
dc.contributor.icrauthorChong, Yu-Shingen


Files in this item

Thumbnail
Thumbnail

This item appears in the following collection(s)

Show simple item record