{"doi":"10.1200/po-25-01017","title":"Systematic Review: Prognostic Molecular Biomarkers in Wilms Tumors","abstract":"<jats:sec>\n                    <jats:title>PURPOSE</jats:title>\n                    <jats:p>Molecular biomarkers are increasingly used for risk stratification, particularly in up-front surgery settings (Children's Oncology Group trials), whereas in preoperative chemotherapy setting, the ongoing International Society of Pediatric Oncology (SIOP)-Renal Tumor Study Group-2016 UMBRELLA study aims to validate selected biomarkers for future risk-adapted treatment strategies. This systematic review summarizes all literature on the prognostic value of these biomarkers.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>MATERIALS AND METHODS</jats:title>\n                    <jats:p>\n                      A systematic literature review (PubMed and Embase; up to January 2025) included studies with ≥50 de novo Wilms tumors (WTs). Eligible biomarkers included copy number variations; 1q gain, 1p and/or 16q loss of heterozygosity (LOH)/loss, 12 gain, 14q loss, 22 loss, 11p15 LOH/loss of imprinting (LOI), and structural somatic variants (\n                      <jats:italic toggle=\"yes\">TP53</jats:italic>\n                      [and/or 17p loss],\n                      <jats:italic toggle=\"yes\">MYCN</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">FBXW7</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">WT1</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">WTX</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">SIX1/SIX2</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">DROSHA</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">DGCR8</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">AMER1</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CTNNB1</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">GPC3</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">MLLT1</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">DICER1</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">DIS3L2</jats:italic>\n                      ). Outcome included relapse-free survival, event-free survival (EFS), and overall survival (OS). Risk of bias was assessed with quality in prognosis studies tool.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS</jats:title>\n                    <jats:p>\n                      Low-bias multivariable/stratified analyses identified 1q gain as worse EFS and 1p and/or 16q LOH/loss as worse EFS/OS prognostic factors, in up-front nephrectomy settings. Preoperative chemotherapy settings revealed similar trends with lacking significance.\n                      <jats:italic toggle=\"yes\">TP53</jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">MYCN</jats:italic>\n                      were adverse prognostic in univariate analyses. No prognostic data were available for the remaining variants.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION</jats:title>\n                    <jats:p>\n                      1q gain and 1p and/or 16q LOH/loss emerge as independent prognostic biomarkers in up-front nephrectomy settings. Evidence remains limited in preoperative chemotherapy settings, particularly when using SIOP-oriented treatment algorithms. Prognostic value of\n                      <jats:italic toggle=\"yes\">TP53</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">MYCN</jats:italic>\n                      , and 11p15 LOH/LOI warrants further validation in both settings. This highlights the need for adequately powered prospective studies, specifically in the preoperative chemotherapy setting, to establish reliable molecular biomarkers.\n                    </jats:p>\n                  </jats:sec>","journal":"JCO Precision Oncology","year":2026,"id":625275,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":91849,"name":"Patrick Kemmeren","orcid":"0000-0003-2237-7354","position":1,"is_corresponding":false},{"id":1616821,"name":"Daniela Perotti","orcid":"0000-0002-6703-2889","position":2,"is_corresponding":false},{"id":1016150,"name":"Harm van Tinteren","orcid":"0000-0002-4626-8702","position":3,"is_corresponding":false},{"id":1416008,"name":"Arnauld Verschuur","orcid":"0000-0003-1070-4442","position":4,"is_corresponding":false},{"id":1073601,"name":"Filippo Spreafico","orcid":"0000-0002-5587-3509","position":5,"is_corresponding":false},{"id":1073597,"name":"Jesper Brok","orcid":"0000-0003-2576-0228","position":6,"is_corresponding":false},{"id":1616822,"name":"Rhoikos C.J. Furtwängler","orcid":"0000-0002-1967-8343","position":7,"is_corresponding":false},{"id":18828,"name":"Tanzina Chowdhury","orcid":null,"position":8,"is_corresponding":false},{"id":1616823,"name":"Reem Al-Saadi","orcid":null,"position":9,"is_corresponding":false},{"id":1616824,"name":"Gordan M. Vujanic","orcid":"0000-0003-0726-6939","position":10,"is_corresponding":false},{"id":1576148,"name":"Amy L. Treece","orcid":null,"position":11,"is_corresponding":false},{"id":258124,"name":"Jarno Drost","orcid":"0000-0002-2941-6179","position":12,"is_corresponding":false},{"id":1616825,"name":"Martine van Grotel","orcid":"0000-0002-8849-8573","position":13,"is_corresponding":false},{"id":72710,"name":"Elizabeth A. Mullen","orcid":"0000-0002-6704-0002","position":14,"is_corresponding":false},{"id":1054888,"name":"Nicholas F. Evageliou","orcid":"0000-0002-5567-0007","position":15,"is_corresponding":false},{"id":552512,"name":"Norbert Graf","orcid":"0000-0002-2248-323X","position":16,"is_corresponding":false},{"id":72711,"name":"Andrew L. Hong","orcid":"0000-0003-0374-1667","position":17,"is_corresponding":false},{"id":1416009,"name":"Manfred Gessler","orcid":"0000-0002-7915-6045","position":18,"is_corresponding":false},{"id":342739,"name":"James I. Geller","orcid":"0000-0001-5181-116X","position":19,"is_corresponding":false},{"id":653751,"name":"Marry M. van den Heuvel‐Eibrink","orcid":"0000-0002-7760-879X","position":20,"is_corresponding":false},{"id":1616820,"name":"Agustina Oller","orcid":"0000-0001-8183-3167","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Systematic Review: Prognostic Molecular Biomarkers in Wilms Tumors","abstract":"<jats:sec>\n                    <jats:title>PURPOSE</jats:title>\n                    <jats:p>Molecular biomarkers are increasingly used for risk stratification, particularly in up-front surgery settings (Children's Oncology Group trials), whereas in preoperative chemotherapy setting, the ongoing International Society of Pediatric Oncology (SIOP)-Renal Tumor Study Group-2016 UMBRELLA study aims to validate selected biomarkers for future risk-adapted treatment strategies. This systematic review summarizes all literature on the prognostic value of these biomarkers.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>MATERIALS AND METHODS</jats:title>\n                    <jats:p>\n                      A systematic literature review (PubMed and Embase; up to January 2025) included studies with ≥50 de novo Wilms tumors (WTs). Eligible biomarkers included copy number variations; 1q gain, 1p and/or 16q loss of heterozygosity (LOH)/loss, 12 gain, 14q loss, 22 loss, 11p15 LOH/loss of imprinting (LOI), and structural somatic variants (\n                      <jats:italic toggle=\"yes\">TP53</jats:italic>\n                      [and/or 17p loss],\n                      <jats:italic toggle=\"yes\">MYCN</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">FBXW7</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">WT1</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">WTX</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">SIX1/SIX2</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">DROSHA</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">DGCR8</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">AMER1</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CTNNB1</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">GPC3</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">MLLT1</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">DICER1</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">DIS3L2</jats:italic>\n                      ). Outcome included relapse-free survival, event-free survival (EFS), and overall survival (OS). Risk of bias was assessed with quality in prognosis studies tool.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS</jats:title>\n                    <jats:p>\n                      Low-bias multivariable/stratified analyses identified 1q gain as worse EFS and 1p and/or 16q LOH/loss as worse EFS/OS prognostic factors, in up-front nephrectomy settings. Preoperative chemotherapy settings revealed similar trends with lacking significance.\n                      <jats:italic toggle=\"yes\">TP53</jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">MYCN</jats:italic>\n                      were adverse prognostic in univariate analyses. No prognostic data were available for the remaining variants.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION</jats:title>\n                    <jats:p>\n                      1q gain and 1p and/or 16q LOH/loss emerge as independent prognostic biomarkers in up-front nephrectomy settings. Evidence remains limited in preoperative chemotherapy settings, particularly when using SIOP-oriented treatment algorithms. Prognostic value of\n                      <jats:italic toggle=\"yes\">TP53</jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">MYCN</jats:italic>\n                      , and 11p15 LOH/LOI warrants further validation in both settings. This highlights the need for adequately powered prospective studies, specifically in the preoperative chemotherapy setting, to establish reliable molecular biomarkers.\n                    </jats:p>\n                  </jats:sec>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"42150146","pmcid":"PMC13193183","openalex_id":"https://openalex.org/W7161594898","authors":[],"funders":[],"total_grants":0,"fwci":3.2141,"citation_percentile":0.92967033,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"hybrid","license":"cc-by-nc-nd","oa_locations":[{"url":"https://ascopubs.org/doi/pdf/10.1200/PO-25-01017","host_type":"journal"},{"url":"https://ascopubs.org/doi/pdf/10.1200/PO-25-01017","host_type":"publisher"},{"url":"https://ascopubs.org/doi/pdfdirect/10.1200/PO-25-01017","host_type":"publisher"},{"url":"https://doi.org/10.1200/po-25-01017","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/42150146","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13193183/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC13193183","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC13193183?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Renal and related cancers","Renal cell carcinoma treatment","Hedgehog Signaling Pathway Studies","Humans","Wilms Tumor","Prognosis","Biomarkers, Tumor","Kidney Neoplasms","Loss of Heterozygosity"],"mesh_terms":["Humans","Kidney Neoplasms","Wilms Tumor","Prognosis","Biomarkers, Tumor","Loss of Heterozygosity"],"keywords":["Wilms' tumor","Chemotherapy","Univariate analysis","Loss of heterozygosity","Overall survival","Nephrectomy","Cancer","Systematic review","Wilms tumour"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Partnerships for the goals"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"},{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T06:19:35.967257Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}