Renal tumors in children and the role of (epi)genetic predisposition

Renal tumors account for ~5% of all childhood cancer diagnoses. Among them, Wilms tumor is by far the most common. In this thesis, we investigated which factors play a role in the development and treatment of childhood renal tumors. Although current Wilms tumor treatment regimens lead to ~90% overall survival rates, they are associated with short- and long-term side effects, and still, not all children with Wilms tumors can be cured. We demonstrated that age is indeed an independent prognostic factor for event-free survival in patients treated with pre-operative chemotherapy. In the future, treatment may be further refined by including age and molecular markers in risk stratification. Furthermore, we investigated the role of (epi)genetic predisposition in a Dutch, nationwide cohort of children with Wilms tumors. Whole exome sequencing (WES) was offered in all cases where no genetic predisposition had been identified by targeted diagnostic testing. Where possible, DNA from resected normal kidney tissue was tested for Beckwith-Wiedemann spectrum, a relatively common Wilms tumor predisposing condition. We determined the prevalence of predisposing factors to be at least 33%, which is higher than previously thought. One of the most remarkable findings was the important contribution of variants in the DIS3L2-gene. Finally, we developed international surveillance guidelines, addressing all currently recognized Wilms tumor predisposition genes and syndromes. Overall, this thesis contributes to understanding relevant clinical, prognostic and underlying (epi)genetic factors in children with renal tumors