Genomes for Kids: The Scope of Pathogenic Mutations in Pediatric Cancer Revealed by Comprehensive DNA and RNA Sequencing.

Autor:	Newman S; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Nakitandwe J; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee., Kesserwan CA; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Azzato EM; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee., Wheeler DA; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Rusch M; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Shurtleff S; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee., Hedges DJ; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Hamilton KV; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Foy SG; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Edmonson MN; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Thrasher A; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Bahrami A; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee., Orr BA; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee., Klco JM; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee., Gu J; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee., Harrison LW; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Wang L; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee., Clay MR; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee., Ouma A; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Silkov A; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Liu Y; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Zhang Z; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Liu Y; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Brady SW; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Zhou X; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Chang TC; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Pande M; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Davis E; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Becksfort J; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Patel A; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Wilkinson MR; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Rahbarinia D; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Kubal M; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Maciaszek JL; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee., Pastor V; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Knight J; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Gout AM; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Wang J; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Gu Z; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee., Mullighan CG; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee., McGee RB; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Quinn EA; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Nuccio R; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Mostafavi R; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Gerhardt EL; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Taylor LM; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Valdez JM; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Hines-Dowell SJ; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Pappo AS; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Robinson G; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Johnson LM; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Pui CH; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee., Ellison DW; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee., Downing JR; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee., Zhang J; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee., Nichols KE; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Jazyk:	angličtina
Zdroj:	Cancer discovery [Cancer Discov] 2021 Dec 01; Vol. 11 (12), pp. 3008-3027.
DOI:	10.1158/2159-8290.CD-20-1631
Abstrakt:	Genomic studies of pediatric cancer have primarily focused on specific tumor types or high-risk disease. Here, we used a three-platform sequencing approach, including whole-genome sequencing (WGS), whole-exome sequencing (WES), and RNA sequencing (RNA-seq), to examine tumor and germline genomes from 309 prospectively identified children with newly diagnosed (85%) or relapsed/refractory (15%) cancers, unselected for tumor type. Eighty-six percent of patients harbored diagnostic (53%), prognostic (57%), therapeutically relevant (25%), and/or cancer-predisposing (18%) variants. Inclusion of WGS enabled detection of activating gene fusions and enhancer hijacks (36% and 8% of tumors, respectively), small intragenic deletions (15% of tumors), and mutational signatures revealing of pathogenic variant effects. Evaluation of paired tumor-normal data revealed relevance to tumor development for 55% of pathogenic germline variants. This study demonstrates the power of a three-platform approach that incorporates WGS to interrogate and interpret the full range of genomic variants across newly diagnosed as well as relapsed/refractory pediatric cancers. Significance: Pediatric cancers are driven by diverse genomic lesions, and sequencing has proven useful in evaluating high-risk and relapsed/refractory cases. We show that combined WGS, WES, and RNA-seq of tumor and paired normal tissues enables identification and characterization of genetic drivers across the full spectrum of pediatric cancers. This article is highlighted in the In This Issue feature, p. 2945. (©2021 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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