dc.date.accessioned | 2018-07-17T09:27:06Z | |
dc.date.issued | 2014-10-01 | |
dc.identifier | http://www.plosone.org/article/info%3Adoi/10.1371/journal.pone.0109924 | |
dc.identifier.citation | PLOS ONE, 2014, 9 (10) | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/2083 | |
dc.description.abstract | Purpose: The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information. Patients and Methods: We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. Results: From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26-16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36-31.7) compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes. Conclusion: This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker. | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | CIRCULAR BINARY SEGMENTATION P53 GENE-MUTATIONS CANCER-STUDY-GROUP ARRAY CGH DATA FAVORABLE HISTOLOGY GENOMIC INSTABILITY PROGNOSTIC-FACTOR POOR-PROGNOSIS MUTANT P53 STAGE-I Multidisciplinary Sciences | |
dc.title | TP53 Mutational Status Is a Potential Marker for Risk Stratification in Wilms Tumour with Diffuse Anaplasia | |
dc.type | Journal Article | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2014-10 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | PLOS ONE | |
pubs.issue | 10 | |
pubs.notes | ISI Document Delivery No.: AR5ZW Times Cited: 0 Cited Reference Count: 47 Maschietto, Mariana Williams, Richard D. Chagtai, Tasnim Popov, Sergey D. Sebire, Neil J. Vujanic, Gordan Perlman, Elizabeth Anderson, James R. Grundy, Paul Dome, Jeffrey S. Pritchard-Jones, Kathy Cancer Research UK [C1188/A11859]; European Commission [FP7-ICT-2009-6]; National Institute for Health Research Great Ormond Street Hospital UCL Biomedical Research Centre award; Great Ormond Street Hospital for Children's Charitable funds; Cancer Research UK; CCLG; National Institutes of Health [CA-42326]; National Wilms Tumor Study Group Late Effects Study [CA-54498]; Children's Oncology Group [CA-98543, CA-98413] This study was funded by Cancer Research UK (Grant No. C1188/A11859) and the European Commission Framework Programme 7 P-medicine integrated project (Grant No. FP7-ICT-2009-6) and supported by the National Institute for Health Research Great Ormond Street Hospital UCL Biomedical Research Centre award and Great Ormond Street Hospital for Children's Charitable funds. The Children's Cancer and Leukaemia Group (CCLG) Tissue Bank is funded by Cancer Research UK and CCLG (www.cclg.org.uk). The research was also supported by grants from the National Institutes of Health to the National Wilms Tumor Study Group (CA-42326), the National Wilms Tumor Study Group Late Effects Study (CA-54498), and the Children's Oncology Group (CA-98543 and CA-98413). The funders had no role in study, design, data collection and analysis, decision to publish, or preparation of the manuscript. 0 PUBLIC LIBRARY SCIENCE SAN FRANCISCO PLOS ONE | |
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/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
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/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team | |
pubs.volume | 9 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Glioma Team | |
dc.contributor.icrauthor | Popov, Sergey | |