Abstract
The Zero Childhood Cancer Program is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Using tumor and germline whole genome sequencing (WGS) and RNA sequencing (RNAseq) across 252 tumors from high-risk pediatric patients with cancer, we identified 968 reportable molecular aberrations (39.9% in WGS and RNAseq, 35.1% in WGS only and 25.0% in RNAseq only). Of these patients, 93.7% 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 central nervous system tumors, methylome analysis confirmed diagnosis in 71.1% of patients and contributed to a change of diagnosis in two patients (2.6%). To date, 43 patients have received a recommended therapy, 38 of whom could be evaluated, with 31% showing objective evidence of clinical benefit. Comprehensive molecular profiling resolved the molecular basis of virtually all high-risk cancers, leading to clinical benefit in some patients.
Original language | English |
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Pages (from-to) | 1742-1753 |
Number of pages | 12 |
Journal | Nature Medicine |
Volume | 26 |
Issue number | 11 |
DOIs | |
Publication status | Published or Issued - Nov 2020 |
Externally published | Yes |
Keywords
- Adolescent
- Child
- Child, Preschool
- DNA Methylation/genetics
- Epigenome/genetics
- Female
- Humans
- Infant
- Male
- Mutation/genetics
- Neoplasm Proteins/genetics
- Neoplasms/classification
- Pediatrics
- Precision Medicine
- Risk Factors
- Transcriptome/genetics
- Whole Exome Sequencing
- Whole Genome Sequencing