| Affiliation: | 1. Department of Pediatric Oncology and Hematology, Saarland University, Homburg, Germany;2. Department of Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada;3. Department of Pathology, Children's Hospital Colorado Anschutz Medical Campus, Aurora, Colorado, USA;4. Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA;5. Wellcome Sanger Institute, Hinxton, UK;6. Molecular Bases of Genetic Risk and Genetic Testing Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;7. Division of Urology, Seattle Children's Hospital, Seattle, Washington, USA Department of Urology, University of Washington, Seattle, Washington, USA;8. Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands;9. Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee, USA |
| Abstract: | Approximately 5% of patients with Wilms tumor present with synchronous bilateral disease. The development of synchronous bilateral Wilms tumor (BWT) is highly suggestive of a genetic or epigenetic predisposition. Patients with known germline predisposition to Wilms tumor (WT1 variants, Beckwith Wiedemann spectrum, TRIM28 variants) have a higher incidence of BWT. This Children's Oncology Group (COG)-International Society for Pediatric Oncology (SIOP-) HARMONICA initiative review for pediatric renal tumors details germline genetic and epigenetic predisposition to BWT development, with an emphasis on alterations in 11p15.5 (ICR1 gain of methylation, paternal uniparental disomy, and postzygotic somatic mosaicism), WT1, TRIM28, and REST. Molecular mechanisms that result in BWT are often also present in multifocal Wilms tumor (multiple separate tumors in one or both kidneys). We identify priority areas for international collaborative research to better understand how predisposing genetic or epigenetic factors associate with response to neoadjuvant chemotherapy, oncologic outcomes, and long-term renal function outcomes. |
