Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

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


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.

Type Journal
ISBN 1546-170X (Electronic) 1078-8956 (Linking)
Authors Wong, M.; Mayoh, C.; Lau, L. M. S.; Khuong-Quang, D. A.; Pinese, M.; Kumar, A.; Barahona, P.; Wilkie, E. E.; Sullivan, P.; Bowen-James, R.; Syed, M.; Martincorena, I.; Abascal, F.; Sherstyuk, A.; Bolanos, N. A.; Baber, J.; Priestley, P.; Dolman, M. E. M.; Fleuren, E. D. G.; Gauthier, M. E.; Mould, E. V. A.; Gayevskiy, V.; Gifford, A. J.; Grebert-Wade, D.; Strong, P. A.; Manouvrier, E.; Warby, M.; Thomas, D. M.; Kirk, J.; Tucker, K.; O'Brien, T.; Alvaro, F.; McCowage, G. B.; Dalla-Pozza, L.; Gottardo, N. G.; Tapp, H.; Wood, P.; Khaw, S. L.; Hansford, J. R.; Moore, A. S.; Norris, M. D.; Trahair, T. N.; Lock, R. B.; Tyrrell, V.; Haber, M.; Marshall, G. M.; Ziegler, D. S.; Ekert, P. G.; Cowley, M. J.
Responsible Garvan Author Prof David Thomas
Published Date 2020-11-01
Published Volume 26
Published Issue 11
Published Pages 1742-1753
Status Published in-print
DOI 10.1038/s41591-020-1072-4
URL link to publisher's version