% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Williams:127794, author = {R. D. Williams and T. Chagtai and M. Alcaide-German and J. Apps and J. Wegert and S. Popov and G. Vujanic and H. van Tinteren and M. M. van den Heuvel-Eibrink and M. Kool$^*$ and J. de Kraker and D. Gisselsson and N. Graf and M. Gessler and K. Pritchard-Jones}, title = {{M}ultiple mechanisms of {MYCN} dysregulation in {W}ilms tumour.}, journal = {OncoTarget}, volume = {6}, number = {9}, issn = {1949-2553}, address = {[S.l.]}, publisher = {Impact Journals LLC}, reportid = {DKFZ-2017-03816}, pages = {7232 - 7243}, year = {2015}, 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.}, keywords = {Proto-Oncogene Proteins c-myc (NLM Chemicals) / TP53 protein, human (NLM Chemicals) / Tumor Suppressor Protein p53 (NLM Chemicals)}, cin = {B062}, ddc = {610}, cid = {I:(DE-He78)B062-20160331}, pnm = {312 - Functional and structural genomics (POF3-312)}, pid = {G:(DE-HGF)POF3-312}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:25749049}, pmc = {pmc:PMC4466681}, doi = {10.18632/oncotarget.3377}, url = {https://inrepo02.dkfz.de/record/127794}, }