作者
Scott Newman,Joy Nakitandwe,Chimene Kesserwan,Elizabeth M Azzato,David A. Wheeler,Michael Rusch,Sheila A. Shurtleff,Dale 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 A. Ouma,Antonina Silkov,Yanling Liu,Zhaojie Zhang,Yu Liu,Samuel W. Brady,Xin Zhou,Ti-Cheng Chang,Manjusha Pande,Eric Davis,Jared Becksfort,Aman Patel,Mark R. Wilkinson,Delaram Rahbarinia,Manish Kubal,Jamie L. Maciaszek,Victor B Pastor,Jay Knight,Alexander M. Gout,Jian Wang,Zhaohui Gu,Charles G. Mullighan,Rose B. McGee,Emily Quinn,Regina Nuccio,Roya Mostafavi,Elsie L. Gerhardt,Leslie Taylor,Jessica M. Valdez,Stacy Hines-Dowell,Alberto S. Pappo,Giles W. Robinson,Liza-Marie Johnson,Ching-Hon Pui,David W. Ellison,James R. Downing,Jinghui Zhang,Kim E. Nichols
摘要
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 (WGS), exome, and RNA sequencing, 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.