DNA Methylation and Transcriptomic Profiles of Wilms Tumour Reveal New Deregulated Genes and Epigenetic Processes Relevant for Tumour Stratification and Management

Wilms tumour (WT), the most common kidney cancer in children, presents features of altered kidney development and frequently exhibits molecular alterations at the 11p15.5 imprinted locus, affecting the IGF2 and H19 genes, which contribute to tumour growth and may also act as predisposing events that require additional hits for tumour initiation. The epigenetic landscape beyond 11p15.5 suggests diagnostic and prognostic potential, but its link to transcriptomic changes is largely unexplored.

We integrated methylomic and transcriptomic datasets of 27 primary tumours and matched non-neoplastic kidneys. DNA methylation profiling identified around 9,000 differentially methylated CpG sites distinguishing neoplastic from non-neoplastic tissue and other pediatric cancers, thus representing a novel WT-specific epigenetic signature. We found that cases with Imprinting Centre 1 (IC1) gain of methylation exhibited the most extensive epigenetic alterations, LOH tumours showed intermediate changes, whereas regressive tumours with largely normal 11p15.5 status displayed limited methylation abnormalities.