Wilms tumour | Nature Reviews Disease Primers

ABSTRACT Wilms tumour (WT) is a childhood embryonal tumour that is paradigmatic of the intersection between disrupted organogenesis and tumorigenesis. Many WT genes play a critical

(non-redundant) role in early nephrogenesis. Improving patient outcomes requires advances in understanding and targeting of the multiple genes and cellular control pathways now identified as

active in WT development. Decades of clinical and basic research have helped to gradually optimize clinical care. Curative therapy is achievable in 90% of affected children, even those with

disseminated disease, yet survival disparities within and between countries exist and deserve commitment to change. Updated epidemiological studies have also provided novel insights into

global incidence variations. Introduction of biology-driven approaches to risk stratification and new drug development has been slower in WT than in other childhood tumours. Current

prognostic classification for children with WT is grounded in clinical and pathological findings and in dedicated protocols on molecular alterations. Treatment includes conventional

cytotoxic chemotherapy and surgery, and radiation therapy in some cases. Advanced imaging to capture tumour composition, optimizing irradiation techniques to reduce target volumes, and

evaluation of newer surgical procedures are key areas for future research. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS HALLMARK DISCOVERIES IN THE BIOLOGY OF NON-WILMS TUMOUR CHILDHOOD KIDNEY CANCERS

Article 29 January 2025 CLINICALLY AND BIOLOGICALLY RELEVANT SUBGROUPS OF WILMS TUMOUR DEFINED BY GENOMIC AND EPIGENOMIC ANALYSES Article Open access 05 October 2020 HALLMARK DISCOVERIES IN

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(2020). PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS The authors thank both the SIOP Renal Tumour Study Group and the Children’s Oncology Group Renal Tumour Committee for

their collective expertise. Their work laid the foundations for this Review article. The authors also thank parents and survivors of childhood Wilms tumour for their contribution to setting

research priorities. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Medical Oncology and Hematology, Paediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori,

Milan, Italy Filippo Spreafico * Department of Paediatrics, IWK Health, Dalhousie University, Halifax, Nova Scotia, Canada Conrad V. Fernandez * Department of Paediatric Haematology and

Oncology, Rigshospitalet, Copenhagen, Denmark Jesper Brok * Cancer Control Center, Osaka International Cancer Institute, Osaka, Japan Kayo Nakata * Department of Pathology, Sidra Medicine,

Doha, Qatar Gordan Vujanic * Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Cincinnati, OH, USA James I. Geller * Theodor-Boveri-Institute,

Developmental Biochemistry, and Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg, Germany Manfred Gessler * Research Center, Boldrini Children’s Hospital, Genetics

and Molecular Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil Mariana Maschietto * Wellcome Sanger Institute, Hinxton, UK Sam Behjati * Cambridge

University Hospitals NHS Foundation Trust, Cambridge, UK Sam Behjati * Department of Paediatrics, University of Cambridge, Cambridge, UK Sam Behjati * National Cancer Research Institute

Children’s Group Consumer Representative, London, UK Angela Polanco * Department of Child Health, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology,

Kumasi, Ghana Vivian Paintsil * Division of Hematology, Oncology and Bone Marrow Transplantation, Department of Paediatrics, University of Colorado, Aurora, CO, USA Sandra Luna-Fineman *

Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK Kathy Pritchard-Jones Authors *

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inPubMed Google Scholar CONTRIBUTIONS Introduction (F.S. and K.P.-J.); Epidemiology (F.S., K.P.-J. and K.N.); Mechanisms/pathophysiology (F.S., K.P.-J., M.G., M.M. and S.B.); Diagnosis,

screening and prevention (F.S., K.P-J., C.V.F., J.B., S.L.-F. and G.V.); Management (F.S., C.V.F., K.P.-J., S.L.-F. and V.P.); Quality of life (F.S., K.P.-J. and A.P.); Outlook (F.S.,

K.P.-J., C.V.F., J.B., M.G., S.L.-F. and J.I.G.); Overview of the Primer (F.S. and K.P.-J.). CORRESPONDING AUTHOR Correspondence to Filippo Spreafico. ETHICS DECLARATIONS COMPETING INTERESTS

All authors declare no competing interests. ADDITIONAL INFORMATION PEER REVIEWER INFORMATION _Nature Reviews Disease Primers_ thanks R. Furtwängler, N. Cost, J. Kalapurakal and the other

anonymous reviewer(s) for their contribution to the peer review of this work. PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps and

institutional affiliations. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION GLOSSARY * Nephron-sparing surgery An operation to remove a kidney tumour by removing only part of the

surrounding normal renal parenchyma. * Nephrogenic rests Abnormally persistent foci of embryonal cells regarded as precursor lesions of Wilms tumour. Rests are subdivided into two main

types: perilobar, confined to the periphery of the renal lobe, and intralobar, found anywhere within the renal lobe. * Overgrowth syndromes A heterogeneous group of disorders in which the

main characteristic is that weight, height or head circumference is two to three standard deviations above the mean for sex and age. The different presentations are dependent on the

developmental pathways and organ systems affected. * Aniridia A rare condition characterized by a partial or complete absence of the iris of the eye. * Nephrotic syndrome A rare clinical

disorder defined by massive proteinuria (>40 mg/m2 per hour) responsible for hypoalbuminaemia (<25 g/l), with resulting hyperlipidaemia, oedema, and various complications. * WAGR

syndrome A rare contiguous gene deletion syndrome (Wilms tumour (WT), aniridia, genitourinary anomalies, and range of developmental delays) associated with a 45–60% risk of developing WT. *

Hypospadias An anatomical congenital malformation of the male external genitalia, characterized by abnormal development of the urethral fold and the ventral foreskin of the penis that causes

abnormal positioning of the urethral opening. * Cryptorchidism The absence of at least one testicle from the scrotum. * Denys–Drash syndrome A rare condition caused by mutations in the

tumour-suppressor gene _WT1_, characterized by a triad of disorders: ambiguous genitalia, nephrotic syndrome leading to end-stage renal disease, and Wilms tumour. * Frasier syndrome A rare

autosomal recessive disorder that presents with male pseudohermaphroditism with gonadal dysgenesis, renal failure in early adulthood and increased risk of developing gonadoblastoma. *

Chromothripsis A catastrophic chromosomal shattering event associated with random rejoining. * Li–Fraumeni syndrome An inherited autosomal dominant cancer predisposition disorder that is

usually associated with abnormalities in _TP53_ located on chromosome 17p13. * Anaplasia Cells with hyperchromatic, pleomorphic nuclei that are three times larger than adjacent cells and

have abnormal mitotic figures. Anaplasia is associated with a poor response to chemotherapy. * Oophorectomy A surgical procedure to remove one or both ovaries. RIGHTS AND PERMISSIONS

Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Spreafico, F., Fernandez, C.V., Brok, J. _et al._ Wilms tumour. _Nat Rev Dis Primers_ 7, 75 (2021).

https://doi.org/10.1038/s41572-021-00308-8 Download citation * Accepted: 14 September 2021 * Published: 14 October 2021 * DOI: https://doi.org/10.1038/s41572-021-00308-8 SHARE THIS ARTICLE

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