Multiple mechanisms of MYCN dysregulation in Wilms tumour

摘要: 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 Wilms tumour (WT), demonstrating that this anaplasia and poorer relapse-free overall survival, independent histology. Using whole exome gene-specific sequencing, together methylation expression profiling, show targeted by other mechanisms, including recurrent somatic mutation, P44L, specific DNA hypomethylation events overexpression tumours high risk histologies. We describe parallel evolution genomic point mutation contralateral remarkable bilateral case which mutations TP53 also evolve over time. report second germline aberration. Our results suggest significant role for dysregulation molecular biology tumour. conclude prognostically significant, novel P44L variant likely to be an activating mutation.