Wilm's Tumor Contributors Unearthed With Sequencing, Epigenetic Analyses

Researchers in Denmark and Italy explore genetic and epigenetic contributors to a type of pediatric kidney cancer known as Wilm's tumor (WT) in a paper appearing in the Journal of Medical Genetics. With the help of whole-genome sequencing, pyrosequencing, and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), the team searched for WT contributors in 24 affected children from Denmark, who were prospectively enrolled in the study between 2016 and 2021. Their search highlighted pathogenic germline variants in the known WT risk genes FBXW7, WT1, or REST in three female patients, while the epigenetic analysis found a single female patient with both chromosome 11 uniparental disomy and Beckwith-Wiedemann syndrome (BWS). Among other BWS-related features, the authors saw enhanced methylation at an imprinting site previously linked to BWS in children with WT compared to their unaffected counterparts, as well as an overrepresentation in alterations affecting the early stages of kidney development. "[C]ombined genomics and epigenetics directly detected the etiology in 17 percent of children with WT," the authors report, noting that "in our study, the majority of the females with WT evidently had an underlying (epi)genetic condition."