A244: Multiregion copy number analysis reveals Wilms’ tumour genetic heterogeneity

George Cresswell1,Borbala Mifsud1,John Apps2,3,Richard Williams2,3,Oystein Olsen3,Kathy Pritchard-Jones2,3,William Mifsud2,3,Nicholas M. Luscombe1

1The Francis Crick Institute, London, UK,2UCL Institute of Child Health, London, UK,3Great Ormond Street Hospital, London, UK

Presenting date: Monday 2 November
Presenting time: 16.10 - 16.25


Understanding genetic heterogeneity in cancers, as well as their clonal evolution, allows us to understand biomarkers in the context of cancer development. Copy number variations (CNVs) can be used to track evolutionary events in cancers. We investigated genetic heterogeneity in the paediatric cancer Wilms’ tumour by obtaining copy number profiles from multiple tumour regions. By comparing these profiles we were able to infer tumour evolution.


Multiple snap-frozen samples were obtained from consecutive post-chemotherapy Wilms’ tumour nephrectomy specimens at Great Ormond Street Hospital, May 2011-June 2013. The extracted DNA was analysed using Illumina CytoSNP-12 arrays for CNV and allelic imbalance. We used R and Bioconductor packages to estimate aberrant cell fraction, segment the genome into regions of CNV across samples and to calculate allele specific copy numbers per region. MEDICC was used to perform intra-patient phylogenetic analysis of tumours.


102 arrays from 21 Wilms’ tumours were analysed in this study. We developed a robust analysis pipeline to identify comparable copy number changes across multiple tumour samples and assess phylogenetic relationships in our dataset. We found that all prospective Wilms’ tumour biomarkers are variably heterogeneous. Furthermore, inferring clonal evolution highlights some well-characterised copy number changes as consistent early events in Wilms’ tumourigenesis. Finally, Wilms’ tumour phylogenetics potentially explain spatially different treatment response and histological heterogeneity.


Using a curated bioinformatics analysis we describe the genetic heterogeneity and evolutionary patterns of 21 Wilms’ tumours. Overall, Wilms’ tumours show a large variation in general patterns of genetic heterogeneity that may provide insight into future patient stratification. As well as describing these patterns, we also categorise important copy number alterations as early or late events in Wilms’ tumourigenesis. This has implications for both understanding Wilms’ tumourigenesis and choosing the appropriate strategy for genetic characterisation of this cancer in future clinical trials.