dc.contributor.author | Little, SE | |
dc.contributor.author | Bax, DA | |
dc.contributor.author | Rodriguez-Pinilla, M | |
dc.contributor.author | Natrajan, R | |
dc.contributor.author | Messahel, B | |
dc.contributor.author | Pritchard-Jones, K | |
dc.contributor.author | Vujanic, GM | |
dc.contributor.author | Reis-Filho, JS | |
dc.contributor.author | Jones, C | |
dc.date.accessioned | 2018-06-27T08:37:07Z | |
dc.date.issued | 2007-08 | |
dc.identifier.citation | Clinical cancer research : an official journal of the American Association for Cancer Research, 2007, 13 (15 Pt 1), pp. 4360 - 4364 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1939 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.ccr-07-0398 | |
dc.description.abstract | Purpose 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.format | Print-Electronic | |
dc.format.extent | 4360 - 4364 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.subject | Humans | |
dc.subject | Nephroma, Mesoblastic | |
dc.subject | Rhabdoid Tumor | |
dc.subject | Sarcoma, Clear Cell | |
dc.subject | Kidney Neoplasms | |
dc.subject | Immunoenzyme Techniques | |
dc.subject | Tissue Array Analysis | |
dc.subject | In Situ Hybridization | |
dc.subject | Signal Transduction | |
dc.subject | Gene Amplification | |
dc.subject | Phosphorylation | |
dc.subject | Mutation | |
dc.subject | Child, Preschool | |
dc.subject | Infant | |
dc.subject | Wilms Tumor | |
dc.subject | Proto-Oncogene Proteins c-akt | |
dc.subject | PTEN Phosphohydrolase | |
dc.subject | ErbB Receptors | |
dc.title | Multifaceted dysregulation of the epidermal growth factor receptor pathway in clear cell sarcoma of the kidney. | |
dc.type | Journal Article | |
rioxxterms.versionofrecord | 10.1158/1078-0432.ccr-07-0398 | |
rioxxterms.licenseref.startdate | 2007-08 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Clinical cancer research : an official journal of the American Association for Cancer Research | |
pubs.issue | 15 Pt 1 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 13 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Functional Genomics | en_US |
icr.researchteam | Glioma Team | en_US |
dc.contributor.icrauthor | Reis-Filho, Jorge Sergio | en |
dc.contributor.icrauthor | Jones, Chris | en |
dc.contributor.icrauthor | Natrajan, Rachael | en |