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dc.date.accessioned2018-07-17T09:22:45Z
dc.date.issued2015-02-01
dc.identifierhttp://genomemedicine.com/content/7/1/11
dc.identifier.citationGenome Medicine, 2015, 7
dc.identifier.issn1756-994X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2082
dc.description.abstractBackground: Wilms tumours (WTs) are characterised by several hallmarks that suggest epimutations such as aberrant DNA methylation are involved in tumour progression: loss of imprinting at 11p15, lack of recurrent mutations and formation of nephrogenic rests (NRs), which are lesions of retained undifferentiated embryonic tissue that can give rise to WTs. Methods: To identify such epimutations, we performed a comprehensive methylome analysis on 20 matched trios of micro-dissected WTs, NRs and surrounding normal kidneys (NKs) using Illumina Infinium HumanMethylation450 Bead Chips and functionally validated findings using RNA sequencing. Results: Comparison of NRs with NK revealed prominent tissue biomarkers: 629 differentially methylated regions, of which 55% were hypermethylated and enriched for domains that are bivalent in embryonic stem cells and for genes expressed during development (P = 2.49 x 10(-5)). Comparison of WTs with NRs revealed two WT subgroups; group-2 WTs and NRs were epigenetically indistinguishable whereas group-1 WTs showed an increase in methylation variability, hypomethylation of renal development genes, hypermethylation and relative loss of expression of cell adhesion genes and known and potential new WT tumour suppressor genes (CASP8, H19, MIR195, RB1 and TSPAN32) and was strongly associated with bilateral disease (P = 0.032). Comparison of WTs and NRs to embryonic kidney highlighted the significance of polycomb target methylation in Wilms tumourigenesis. Conclusions: Methylation levels vary during cancer evolution. We have described biomarkers related to WT evolution from its precursor NRs which may be useful to differentiate between these tissues for patients with bilateral disease.
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectEMBRYONIC STEM-CELLS CPG ISLAND SHORES DIFFERENTIAL METHYLATION PROMOTER METHYLATION EPIGENETIC CHANGES GENE-EXPRESSION CANCER MUTATIONS DFNA5 WT1
dc.titleComparative methylome analysis identifies new tumour subtypes and biomarkers for transformation of nephrogenic rests into Wilms tumour
dc.typeJournal Article
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2015-02
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfGenome Medicine
pubs.notesISI Document Delivery No.: CC8AN Times Cited: 0 Cited Reference Count: 55 Charlton, Jocelyn Williams, Richard D. Sebire, Neil J. Popov, Sergey Vujanic, Gordan Chagtai, Tasnim Alcaide-German, Marisa Morris, Tiffany Butcher, Lee M. Guilhamon, Paul Beck, Stephan Pritchard-Jones, Kathy UCL Grand Challenges Scheme; Olivia Hodson fund; Cancer Research UK [C1188/A4614]; Great Ormond Street Hospital (GOSH) Children's Charity and Children with Cancer [11MH16]; EU [261474, 259679, 257082, 282510]; NIHR GOSH UCL Biomedical Research Centre; Wellcome Trust [99148]; UCL Biomedical Research Centre [BRC84/CN/SB/5984]; Royal Society Wolfson Research Merit Award [WM100023]; IMI-JU OncoTrack [115234]; Cancer Research UK; MRC/Wellcome Trust [099175/Z/12/Z] JC was funded by the UCL Grand Challenges Scheme and the Olivia Hodson fund. The Pritchard-Jones laboratory was funded by Cancer Research UK (C1188/A4614), Great Ormond Street Hospital (GOSH) Children's Charity and Children with Cancer (11MH16) and EU-FP7 project ENCCA (261474). NJS and KPJ are part supported by the NIHR GOSH UCL Biomedical Research Centre. The Beck laboratory was funded by the Wellcome Trust (99148), the UCL Biomedical Research Centre (BRC84/CN/SB/5984), a Royal Society Wolfson Research Merit Award (WM100023), IMI-JU OncoTrack (115234) and EU-FP7 projects IDEAL (259679), EPIGENESYS (257082) and BLUEPRINT (282510). The authors would like to thank all the investigators at the contributing Children's Cancer and Leukaemia Group (CCLG) treatment centres and the CCLG tissue bank, which is funded by Cancer Research UK, for provision of samples. We thank Kerra Pearce and Tony Brooks from UCL Genomics for their help with processing the Illumina 450 k arrays and the Illumina sequencing. The human embryonic and foetal material was provided by the Joint MRC/Wellcome Trust (grant number 099175/Z/12/Z) Human Developmental Biology Resource (https://hdbr.org). We would also like to thank Paul Winyard and Karen Price for help with processing the embryonic kidney tissue. 0 BIOMED CENTRAL LTD LONDON GENOME MED
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/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.volume7
pubs.embargo.termsNot known
icr.researchteamGlioma Team
dc.contributor.icrauthorPopov, Sergey


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