ArticleCancer research2021
Genomic and Transcriptomic Analysis of Relapsed and Refractory Childhood Solid Tumors Reveals a Diverse Molecular Landscape and Mechanisms of Immune Evasion.
Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Molecular-guided therapy for the treatment of patients with relapsed and refractory childhood cancers: a Beat Childhood Cancer Research Consortium trial.Genome medicine · 2024Trial
- Immunotherapy for pediatric solid tumors: overcoming biological barriers through rational multimodal combinations.Cancer immunology, immunotherapy : CII · 2026Review
- From classical machine learning to emerging foundation models: review on multimodal data integration for cancer research.Artificial intelligence review · 2026Article
- The Mutational Epidemiology of Childhood Cancer.Clinical chemistry · 2025Review
- HNRNPH1-mediated splicing events regulatebioRxiv : the preprint server for biology · 2025Article
- Gene Expression Analysis of (Paired) Primary and Relapsed Wilms Tumor Samples to Unravel the Underlying Factors Driving Tumor Recurrence.Cancer medicine · 2025Article
- Pediatric tumor microenvironment: developmental dynamics and therapy resistance.Frontiers in oncology · 2025Review
- Article
- Whole-Exome Sequencing Reveals Novel Candidate Driver Mutations and Potential Druggable Mutations in Patients with High-Risk Neuroblastoma.Journal of personalized medicine · 2024Article
- Immune Microenvironment in Childhood Cancers: Characteristics and Therapeutic Challenges.Cancers · 2024Review
- Pediatric Solid Cancers: Dissecting the Tumor Microenvironment to Improve the Results of Clinical Immunotherapy.International journal of molecular sciences · 2024Review
- The clinical utility of integrative genomics in childhood cancer extends beyond targetable mutations.Nature cancer · 2023Article
- Using 3D-bioprinted models to study pediatric neural crest-derived tumors.International journal of bioprinting · 2023Article
- Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program 'iTHER'.European journal of cancer (Oxford, England : 1990) · 2022Article
- Molecular Characterization Reveals Subclasses of 1q Gain in Intermediate Risk Wilms Tumors.Cancers · 2022Article
- The Cellular Tumor Immune Microenvironment of Childhood Solid Cancers: Informing More Effective Immunotherapies.Cancers · 2022Review
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39 authors.
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Abstract
Children with treatment-refractory or relapsed (R/R) tumors face poor prognoses. As the genomic underpinnings driving R/R disease are not well defined, we describe here the genomic and transcriptomic landscapes of R/R solid tumors from 202 patients enrolled in Beat Childhood Cancer Consortium clinical trials. Tumor mutational burden (TMB) was elevated relative to untreated tumors at diagnosis, with one-third of tumors classified as having a pediatric high TMB. Prior chemotherapy exposure influenced the mutational landscape of these R/R tumors, with more than 40% of tumors demonstrating mutational signatures associated with platinum or temozolomide chemotherapy and two tumors showing treatment-associated hypermutation. Immunogenomic profiling found a heterogenous pattern of neoantigen and MHC class I expression and a general absence of immune infiltration. Transcriptional analysis and functional gene set enrichment analysis identified cross-pathology clusters associated with development, immune signaling, and cellular signaling pathways. While the landscapes of these R/R tumors reflected those of their corresponding untreated tumors at diagnosis, important exceptions were observed, suggestive of tumor evolution, treatment resistance mechanisms, and mutagenic etiologies of treatment. SIGNIFICANCE: Tumor heterogeneity, chemotherapy exposure, and tumor evolution contribute to the molecular profiles and increased mutational burden that occur in treatment-refractory and relapsed childhood solid tumors.
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