dc.date.accessioned | 2018-07-17T08:44:27Z | |
dc.date.issued | 2015-03-01 | |
dc.identifier | http://publications.icr.ac.uk/14113/ | |
dc.identifier.citation | Oncotarget, 2015, 6 (9), pp. 7232 - 7243 | |
dc.identifier.issn | 1949-2553 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/2080 | |
dc.description.abstract | Genomic gain of the proto-oncogene transcription factor gene MYCN is associated with poor prognosis in several childhood cancers. Here we present a comprehensive copy number analysis of MYCN in Wilms tumour (WT), demonstrating that gain of this gene is associated with anaplasia and with poorer relapse-free and overall survival, independent of histology. Using whole exome and gene-specific sequencing, together with methylation and expression profiling, we show that MYCN is targeted by other mechanisms, including a recurrent somatic mutation, P44L, and specific DNA hypomethylation events associated with MYCN overexpression in tumours with high risk histologies. We describe parallel evolution of genomic copy number gain and point mutation of MYCN in the contralateral tumours of a remarkable bilateral case in which independent contralateral mutations of TP53 also evolve over time. We report a second bilateral case in which MYCN gain is a germline aberration. Our results suggest a significant role for MYCN dysregulation in the molecular biology of Wilms tumour. We conclude that MYCN gain is prognostically significant, and suggest that the novel P44L somatic variant is likely to be an activating mutation. | |
dc.format.extent | 7232 - 7243 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Wilms tumour MYCN copy number DNA methylation prognostic marker integrative genomics viewer copy-number oncogene amplification somatic mutations sequencing data beta-catenin gene histology reveals gain | |
dc.title | Multiple mechanisms of MYCN dysregulation in Wilms tumour | |
dc.type | Journal Article | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2015-03 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Oncotarget | |
pubs.issue | 9 | |
pubs.notes | ISI Document Delivery No.: CF8GI Times Cited: 0 Cited Reference Count: 54 Williams, Richard D. Chagtai, Tasnim Alcaide-German, Marisa Apps, John Wegert, Jenny Popov, Sergey Vujanic, Gordan van Tinteren, Harm van den Heuvel-Eibrink, Marry M. Kool, Marcel de Kraker, Jan Gisselsson, David Graf, Norbert Gessler, Manfred Pritchard-Jones, Kathy Cancer Research UK [C1188/A4614]; Great Ormond Street Hospital (GOSH) Children's Charity and Children with Cancer [11MH16]; NIHR GOSH UCL Biomedical Research Centre; DFG [Ge539/12-1]; Wilhelm-Sander-Stiftung; Competence Network Paediatric Oncology and Haematology The Pritchard-Jones laboratory is funded by Cancer Research UK (C1188/A4614), Great Ormond Street Hospital (GOSH) Children's Charity and Children with Cancer (11MH16). KPJ is part supported by the NIHR GOSH UCL Biomedical Research Centre. The Gessler laboratory is funded by grants from the DFG (Ge539/12-1), the Wilhelm-Sander-Stiftung and the Competence Network Paediatric Oncology and Haematology. Impact journals llc Albany | |
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 | 6 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Glioma Team | |
dc.contributor.icrauthor | Popov, Sergey | |