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Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancer.

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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Wong M,Mayoh C,Lau LMS,Khuong-Quang DA,Pinese M,Kumar A,Barahona P,Wilkie EE,Sullivan P,Bowen-James R,Syed M,Martincorena I,Abascal F,Sherstyuk A,Bolanos NA,Baber J,Priestley P,Dolman MEM,Fleuren EDG,Gauthier ME,M

doi

10.1038/s41591-020-1072-4

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

1742-1753

issue

11

eissn

1078-8956

issn

1546-170X

pii

10.1038/s41591-020-1072-4

journal_volume

26

pub_type

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