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dc.contributor.authorLittle, SEen_US
dc.contributor.authorBax, DAen_US
dc.contributor.authorRodriguez-Pinilla, Men_US
dc.contributor.authorNatrajan, Ren_US
dc.contributor.authorMessahel, Ben_US
dc.contributor.authorPritchard-Jones, Ken_US
dc.contributor.authorVujanic, GMen_US
dc.contributor.authorReis-Filho, JSen_US
dc.contributor.authorJones, Cen_US
dc.date.accessioned2018-06-27T08:37:07Z
dc.date.issued2007-08en_US
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2007, 13 (15 Pt 1), pp. 4360 - 4364en_US
dc.identifier.issn1078-0432en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1939
dc.identifier.doi10.1158/1078-0432.ccr-07-0398en_US
dc.description.abstractPURPOSE:Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase overexpressed in a variety of human malignancies, against which targeted therapies have shown efficacy in lung and brain tumors. Clinical responses to EGFR inhibitors have been found to be highly dependent on the presence of activating mutations, whereas gene amplification, downstream activation of Akt, and abnormalities in PTEN are also reported predictive factors. We sought to evaluate these variables in pediatric renal tumors. EXPERIMENTAL DESIGN:We screened a series of 307 pediatric renal tumors for EGFR expression by immunohistochemistry and gene amplification by chromogenic in situ hybridization. In identifying a striking predilection for certain tumor types, we further analyzed the clear cell sarcomas of the kidney (CCSK) for mutations in EGFR and PTEN. RESULTS:Although only 23 of 177 (13.0%) nonanaplastic Wilms' tumors were EGFR positive, 4 of 11 (36.4%) anaplastic tumors showed receptor overexpression. In addition, 5 of 9 (55.6%) mesoblastic nephromas and 12 of 12 (100%) CCSKs were strongly immunoreactive for EGFR. In studying the CCSKs in more detail, we identified gene amplification in 1 of 12 (8.3%) cases and a somatic T790M EGFR mutation in a further case. These two samples additionally harbored mutations in PTEN. Downstream pathway activation, as assayed by phosphorylated Akt expression, was observed in 8 of 12 (66.7%) cases. CONCLUSIONS:Together, these data show dysregulation of the EGFR pathway at multiple levels in CCSKs. Identification of factors predictive of poor response to targeted therapy, including the drug resistance T790M mutation, may provide a rationale for upfront trials with irreversible inhibitors of EGFR in children with these tumors.en_US
dc.formatPrint-Electronicen_US
dc.format.extent4360 - 4364en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectHumansen_US
dc.subjectNephroma, Mesoblasticen_US
dc.subjectRhabdoid Tumoren_US
dc.subjectSarcoma, Clear Cellen_US
dc.subjectKidney Neoplasmsen_US
dc.subjectImmunoenzyme Techniquesen_US
dc.subjectTissue Array Analysisen_US
dc.subjectIn Situ Hybridizationen_US
dc.subjectSignal Transductionen_US
dc.subjectGene Amplificationen_US
dc.subjectPhosphorylationen_US
dc.subjectMutationen_US
dc.subjectChild, Preschoolen_US
dc.subjectInfanten_US
dc.subjectWilms Tumoren_US
dc.subjectProto-Oncogene Proteins c-akten_US
dc.subjectPTEN Phosphohydrolaseen_US
dc.subjectErbB Receptorsen_US
dc.titleMultifaceted dysregulation of the epidermal growth factor receptor pathway in clear cell sarcoma of the kidney.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1158/1078-0432.ccr-07-0398en_US
rioxxterms.licenseref.startdate2007-08en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Researchen_US
pubs.issue15 Pt 1en_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/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Molecular Pathology
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/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team
pubs.publication-statusPublisheden_US
pubs.volume13en_US
pubs.embargo.termsNot knownen_US
icr.researchteamFunctional Genomicsen_US
icr.researchteamGlioma Teamen_US
dc.contributor.icrauthorJones, Chrisen_US
dc.contributor.icrauthorReis-Filho, Jorge Sergioen_US
dc.contributor.icrauthorNatrajan, Rachaelen_US


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