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dc.contributor.authorLittle, SE
dc.contributor.authorBax, DA
dc.contributor.authorRodriguez-Pinilla, M
dc.contributor.authorNatrajan, R
dc.contributor.authorMessahel, B
dc.contributor.authorPritchard-Jones, K
dc.contributor.authorVujanic, GM
dc.contributor.authorReis-Filho, JS
dc.contributor.authorJones, C
dc.date.accessioned2018-06-27T08:37:07Z
dc.date.issued2007-08
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2007, 13 (15 Pt 1), pp. 4360 - 4364
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1939
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-07-0398
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.
dc.formatPrint-Electronic
dc.format.extent4360 - 4364
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectNephroma, Mesoblastic
dc.subjectRhabdoid Tumor
dc.subjectSarcoma, Clear Cell
dc.subjectKidney Neoplasms
dc.subjectImmunoenzyme Techniques
dc.subjectTissue Array Analysis
dc.subjectIn Situ Hybridization
dc.subjectSignal Transduction
dc.subjectGene Amplification
dc.subjectPhosphorylation
dc.subjectMutation
dc.subjectChild, Preschool
dc.subjectInfant
dc.subjectWilms Tumor
dc.subjectProto-Oncogene Proteins c-akt
dc.subjectPTEN Phosphohydrolase
dc.subjectErbB Receptors
dc.titleMultifaceted dysregulation of the epidermal growth factor receptor pathway in clear cell sarcoma of the kidney.
dc.typeJournal Article
rioxxterms.versionofrecord10.1158/1078-0432.ccr-07-0398
rioxxterms.licenseref.startdate2007-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Research
pubs.issue15 Pt 1
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/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.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-statusPublished
pubs.volume13
pubs.embargo.termsNot known
icr.researchteamFunctional Genomicsen_US
icr.researchteamGlioma Teamen_US
dc.contributor.icrauthorReis-Filho, Jorge Sergioen
dc.contributor.icrauthorJones, Chrisen
dc.contributor.icrauthorNatrajan, Rachaelen


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