Abstract 7221: Whole genome and transcriptome sequencing can be introduced into the diagnostic workup of sarcoma and pediatric cancer patients

Abstract Introduction: Limited molecular diagnostics in pediatric cancers and sarcomas hinder accurate diagnosis and therapy selection, due to an inability to detect some clinically relevant large and rare rearrangements. This meta-analysis evaluates the potential of WGS/WGTS to overcome these limitations and improve personalized oncology care. Methods: A systematic review and meta-analysis of English-language studies (PubMed; 01/08/2024-5/11/2024) was conducted per PRISMA guidelines to evaluate the clinical impact of WG(T)S in pediatric cancers and sarcomas. Included studies were primary research articles with data on clinical impact, validity, utility, and/or feasibility. Results: A total of 14 studies (5 sarcoma and 9 pediatric) were deemed eligible for inclusion in the study. Analysis revealed a wide turnaround time (TAT) range of 9-71 days. Sequencing depths ranged from 45-100X for tumor and 30-40X for normal samples, whilst feasibility of WG(T)S ranged from 62-100%. Our analysis found that WG(T)S demonstrated significant clinical utility in sarcoma patients leading to a refined/changed diagnosis in 18.6%, actionable findings in 64%, and therapy-informing findings in 36% of cases, on average. In pediatric cancers, WG(T)S led to a refined/changed diagnosis in 22.9%, actionable findings in 42.6%, and therapy-informing findings in 38.5% of cases, on average. We also found that, on average, 7.3% of both sarcoma and pediatric cancer patients harbored germline findings (Table 1). Conclusions: WG(T)S enhances diagnostic yield by detecting large rearrangements (e.g., structural variants, gene fusions) critical for accurate diagnosis and risk stratification in pediatric cancers and sarcomas. Our meta-analysis demonstrates the clinical utility of WG(T)S, suggesting its potential for routine use in oncology. Citation Format: Svetlana Nikic, Kristine N. Jinnett. Whole genome and transcriptome sequencing can be introduced into the diagnostic workup of sarcoma and pediatric cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7221.