Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk paediatric cancer
Zero Childhood Cancer is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Utilising tumour and germline whole genome sequencing (WGS) and RNA sequencing (RNAseq) across 252 tumours from high-risk paediatric cancer patients, we identified 968 reportable molecular aberrations (39.9% in WGS and RNAseq, 35.1% WGS-only, 25.0% RNAseq-only). 93.7% of patients had at least one germline or somatic aberration, 71.4% had therapeutic targets and 5.2% had a change in diagnosis. WGS identified pathogenic cancer-predisposing variants in 16.2% of patients. In 76 CNS tumours, methylome analysis confirmed diagnosis in 71.1% and contributed to a change of diagnosis in two cases (2.6%). To date 43 patients have received a recommended therapy, 38 of whom could be evaluated. A small but encouraging proportion of 31% showed some evidence of clinical benefit. Comprehensive molecular profiling resolved the molecular basis of virtually all high-risk cancers, which in some cases has significant clinical impact.
- Type: Other
- Archiver: European Genome-Phenome Archive (EGA)
Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data
Dataset ID | Description | Technology | Samples |
---|---|---|---|
EGAD00001006876 | NextSeq 500 | 226 | |
EGAD00001006902 | HiSeq X Ten | 480 | |
EGAD00001006906 | 500 | ||
EGAD00001006907 | 500 | ||
EGAD00001006908 | 252 | ||
EGAD00001006909 | 76 | ||
EGAD00001006910 | 247 | ||
EGAD00001008358 | HiSeq X Ten NextSeq 500 | 94 |
Publications | Citations |
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Diffuse leptomeningeal glioneuronal tumour (DLGNT) in children: the emerging role of genomic analysis.
Acta Neuropathol Commun 9: 2021 147 |
10 |
In vitro and in vivo drug screens of tumor cells identify novel therapies for high-risk child cancer.
EMBO Mol Med 14: 2022 e14608 |
16 |
Diagnostic classification of childhood cancer using multiscale transcriptomics.
Nat Med 29: 2023 656-666 |
12 |
A novel transcriptional signature identifies T-cell infiltration in high-risk paediatric cancer.
Genome Med 15: 2023 20 |
4 |
High-Throughput Drug Screening of Primary Tumor Cells Identifies Therapeutic Strategies for Treating Children with High-Risk Cancer.
Cancer Res 83: 2023 2716-2732 |
10 |
Precision-guided treatment in high-risk pediatric cancers.
Nat Med 30: 2024 1913-1922 |
5 |