Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancer.
Nat Med
; 26(11): 1742-1753, 2020 11.
Article
en En
| MEDLINE
| ID: mdl-33020650
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Transcriptoma
/
Epigenoma
/
Proteínas de Neoplasias
/
Neoplasias
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
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Infant
/
Male
Idioma:
En
Revista:
Nat Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Australia