计算生物学
DNA测序
外显子组测序
癌症基因组测序
突变
深度测序
基因组学
全基因组测序
作者
Scott Newman,Joy Nakitandwe,Chimene A. Kesserwan,Elizabeth M. Azzato,David A. Wheeler,Michael Rusch,Sheila Shurtleff,Dale J. Hedges,Kayla V. Hamilton,Scott G. Foy,Michael N. Edmonson,Andrew Thrasher,Armita Bahrami,Brent A. Orr,Jeffery M. Klco,Jiali Gu,Lynn W. Harrison,Lu Wang,Michael R. Clay,Annastasia Ouma
出处
期刊:Cancer Discovery
[American Association for Cancer Research]
日期:2021-07-23
卷期号:11 (12): 3008-3027
被引量:194
标识
DOI:10.1158/2159-8290.cd-20-1631
摘要
Abstract 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
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