Wilms tumour is the most common renal malignancy of childhood. It is curable in the majority of children, albeit at considerable cost in terms of treatment related late effects in some children. In the small group of 'high risk' Wilms tumours, the prognosis is much worse. Overall, one in ten children with Wilms tumour will still die of their disease despite modern treatment approaches.The genetic changes underpinning Wilms tumour have been defined by studies of familial cases and more recently, by unbiased DNA sequencing of tumour genomes. Together these have defined the landscape of cancer genes that are operative in Wilms tumour. Many are intricately linked to control of fetal nephrogenesis. Here, we review our current understanding of germline and somatic genetic changes that underlie Wilms tumour.
A -Introduction
A1. Brief overview 1.1 What is it?Wilms tumour (WT), also known as nephroblastoma, is one of the so-called embryonal tumours of childhood, due to its histological mimicry of stages in nephrogenesis and its early age of onset. It accounts for 90% of childhood renal tumours and constitutes 7% of all childhood cancers(1). Thought to arise from aberrant nephrogenesis, many of the genetic changes underpinning WT occur in genes involved in fetal nephrogenesis(2). Although our understanding of tumourigenesis remains incomplete, the WNT pathway and insulin-like growth factor (IGF) signaling have long been considered to have pathogenic roles. This review follows recent large scale analyses interrogating the somatic basis of WT. The genetic changes underpinning WT are diverse, driven by an array of almost 40 cancer genes (Table 1). Such diversity is particularly surprising given the monotonous driver landscape of other childhood renal tumours, such as clear cell sarcoma of the kidney (CCSK) or congenital mesoblastic nephroma (CMN). In comparison to adult cancers, the median somatic mutation rate is far lower in WT, 0.17 per million bases