中枢神经系统（CNS）肿瘤类型的多样性使得儿童和青少年的患者结果不同，并使准确诊断具有挑战性。在此研究中，我们在一组超过1,200名新诊断的儿科CNS肿瘤患者中，前瞻性地将DNA甲基化谱系分析和靶向基因检测与盲目的神经病理参考诊断相结合，以评估其在常规神经病理学中的实用性。我们表明，多组学集成通过将其注释为精炼的DNA甲基化类（50％），检测诊断或治疗相关的遗传变异（47％）或鉴定癌症易感综合征（10％），在相当比例的患者中提高了诊断准确性。通过神经病理学基于WHO和DNA甲基化基于分类所得出的不一致结果（30％）在组织高级胶质瘤中比较富集，这暗示了对所有患者的当前临床患者管理的相关性为5％。随访（中位数2.5年）显示，具有低级分子表型的组织学高级胶质瘤的患者的生存率有所提高。这些结果为儿科神经肿瘤学中多组学集成在神经病理学中的实用性提供了初步的证据。©2023年作者。

The large diversity of central nervous system (CNS) tumor types in children and adolescents results in disparate patient outcomes and renders accurate diagnosis challenging. In this study, we prospectively integrated DNA methylation profiling and targeted gene panel sequencing with blinded neuropathological reference diagnostics for a population-based cohort of more than 1,200 newly diagnosed pediatric patients with CNS tumors, to assess their utility in routine neuropathology. We show that the multi-omic integration increased diagnostic accuracy in a substantial proportion of patients through annotation to a refining DNA methylation class (50%), detection of diagnostic or therapeutically relevant genetic alterations (47%) or identification of cancer predisposition syndromes (10%). Discrepant results by neuropathological WHO-based and DNA methylation-based classification (30%) were enriched in histological high-grade gliomas, implicating relevance for current clinical patient management in 5% of all patients. Follow-up (median 2.5 years) suggests improved survival for patients with histological high-grade gliomas displaying lower-grade molecular profiles. These results provide preliminary evidence of the utility of integrating multi-omics in neuropathology for pediatric neuro-oncology.© 2023. The Author(s).