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

Marie Wong, Chelsea Mayoh, Loretta M.S. Lau, Dong Anh Khuong-Quang, Mark Pinese, Amit Kumar, Paulette Barahona, Emilie E. Wilkie, Patricia Sullivan, Rachel Bowen-James, Mustafa Syed, Iñigo Martincorena, Federico Abascal, Alexandra Sherstyuk, Noemi A. Bolanos, Jonathan Baber, Peter Priestley, M. Emmy M. Dolman, Emmy D.G. Fleuren, Marie Emilie GauthierEmily V.A. Mould, Velimir Gayevskiy, Andrew J. Gifford, Dylan Grebert-Wade, Patrick A. Strong, Elodie Manouvrier, Meera Warby, David M. Thomas, Judy Kirk, Katherine Tucker, Tracey O’Brien, Frank Alvaro, Geoffry B. McCowage, Luciano Dalla-Pozza, Nicholas G. Gottardo, Heather Tapp, Paul Wood, Seong Lin Khaw, Jordan R. Hansford, Andrew S. Moore, Murray D. Norris, Toby N. Trahair, Richard B. Lock, Vanessa Tyrrell, Michelle Haber, Glenn M. Marshall, David S. Ziegler, Paul G. Ekert, Mark J. Cowley

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

179 Citaten (Scopus)


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.

Originele taal-2Engels
Pagina's (van-tot)1742-1753
Aantal pagina's12
TijdschriftNature Medicine
Nummer van het tijdschrift11
StatusGepubliceerd - nov. 2020
Extern gepubliceerdJa


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