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dc.contributor.authorNg, CKY
dc.contributor.authorMartelotto, LG
dc.contributor.authorGauthier, A
dc.contributor.authorWen, H-C
dc.contributor.authorPiscuoglio, S
dc.contributor.authorLim, RS
dc.contributor.authorCowell, CF
dc.contributor.authorWilkerson, PM
dc.contributor.authorWai, P
dc.contributor.authorRodrigues, DN
dc.contributor.authorArnould, L
dc.contributor.authorGeyer, FC
dc.contributor.authorBromberg, SE
dc.contributor.authorLacroix-Triki, M
dc.contributor.authorPenault-Llorca, F
dc.contributor.authorGiard, S
dc.contributor.authorSastre-Garau, X
dc.contributor.authorNatrajan, R
dc.contributor.authorNorton, L
dc.contributor.authorCottu, PH
dc.contributor.authorWeigelt, B
dc.contributor.authorVincent-Salomon, A
dc.contributor.authorReis-Filho, JS
dc.date.accessioned2020-07-28T13:36:49Z
dc.date.issued2015-05-22
dc.identifier.citationGenome biology, 2015, 16 pp. 107 - ?
dc.identifier.issn1474-7596
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3881
dc.identifier.eissn1474-760X
dc.identifier.doi10.1186/s13059-015-0657-6
dc.description.abstractBACKGROUND: HER2 is overexpressed and amplified in approximately 15% of invasive breast cancers, and is the molecular target and predictive marker of response to anti-HER2 agents. In a subset of these cases, heterogeneous distribution of HER2 gene amplification can be found, which creates clinically challenging scenarios. Currently, breast cancers with HER2 amplification/overexpression in just over 10% of cancer cells are considered HER2-positive for clinical purposes; however, it is unclear as to whether the HER2-negative components of such tumors would be driven by distinct genetic alterations. Here we sought to characterize the pathologic and genetic features of the HER2-positive and HER2-negative components of breast cancers with heterogeneous HER2 gene amplification and to define the repertoire of potential driver genetic alterations in the HER2-negative components of these cases. RESULTS: We separately analyzed the HER2-negative and HER2-positive components of 12 HER2 heterogeneous breast cancers using gene copy number profiling and massively parallel sequencing, and identified potential driver genetic alterations restricted to the HER2-negative cells in each case. In vitro experiments provided functional evidence to suggest that BRF2 and DSN1 overexpression/amplification, and the HER2 I767M mutation may be alterations that compensate for the lack of HER2 amplification in the HER2-negative components of HER2 heterogeneous breast cancers. CONCLUSIONS: Our results indicate that even driver genetic alterations, such as HER2 gene amplification, can be heterogeneously distributed within a cancer, and that the HER2-negative components are likely driven by genetic alterations not present in the HER2-positive components, including BRF2 and DSN1 amplification and HER2 somatic mutations.
dc.formatElectronic
dc.format.extent107 - ?
dc.languageeng
dc.language.isoeng
dc.publisherBMC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectReceptor, erbB-2
dc.subjectTranscription Factor TFIIIB
dc.subjectChromosomal Proteins, Non-Histone
dc.subjectSignal Transduction
dc.subjectGene Amplification
dc.subjectGene Dosage
dc.subjectMutation
dc.subjectFemale
dc.subjectMCF-7 Cells
dc.titleIntra-tumor genetic heterogeneity and alternative driver genetic alterations in breast cancers with heterogeneous HER2 gene amplification.
dc.typeJournal Article
dcterms.dateAccepted2015-04-20
rioxxterms.versionofrecord10.1186/s13059-015-0657-6
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2015-05-22
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfGenome biology
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/Functional Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Functional Genomics
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/Functional Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Functional Genomics
pubs.publication-statusPublished
pubs.volume16
pubs.embargo.termsNot known
icr.researchteamFunctional Genomics
dc.contributor.icrauthorNatrajan, Rachael


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