Genomes for Kids: The scope of pathogenic mutations in pediatric cancer revealed by comprehensive DNA and RNA sequencing
In: Cancer Discov, 2021
academicJournal
Zugriff:
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.
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Genomes for Kids: The scope of pathogenic mutations in pediatric cancer revealed by comprehensive DNA and RNA sequencing
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Autor/in / Beteiligte Person: | Newman, Scott ; Nakitandwe, Joy ; Kesserwan, Chimene A. ; Azzato, Elizabeth M. ; Wheeler, David A. ; Rusch, Michael ; Shurtleff, Sheila ; Hedges, Dale J. ; Hamilton, Kayla V. ; Foy, Scott G. ; Edmonson, Michael N. ; Thrasher, Andrew ; Bahrami, Armita ; Orr, Brent A. ; Klco, Jeffery M. ; Gu, Jiali ; Harrison, Lynn W. ; Wang, Lu ; Clay, Michael R. ; Ouma, Annastasia ; Silkov, Antonina ; Liu, Yanling ; Zhang, Zhaojie ; Liu, Yu ; Brady, Samuel W. ; Zhou, Xin ; Chang, Ti-Cheng ; Pande, Manjusha ; Davis, Eric ; Becksfort, Jared ; Patel, Aman ; Wilkinson, Mark R. ; Rahbarinia, Delaram ; Kubal, Manish ; Maciaszek, Jamie L. ; Pastor, Victor ; Knight, Jay ; Gout, Alexander M. ; Wang, Jian ; Gu, Zhaohui ; Mullighan, Charles G. ; McGee, Rose B. ; Quinn, Emily A. ; Nuccio, Regina ; Mostafavi, Roya ; Gerhardt, Elsie L. ; Taylor, Leslie M. ; Valdez, Jessica M. ; Hines-Dowell, Stacy J. ; Pappo, Alberto S. ; Robinson, Giles ; Johnson, Liza-Marie ; Pui, Ching-Hon ; Ellison, David W. ; Downing, James R. ; Zhang, Jinghui ; Nichols, Kim E. |
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Zeitschrift: | Cancer Discov, 2021 |
Veröffentlichung: | 2021 |
Medientyp: | academicJournal |
DOI: | 10.1158/2159-8290.CD-20-1631 |
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