Synapse - Feasibility of whole genome and transcriptome profiling in pediatric and young adult cancers

Feasibility of whole genome and transcriptome profiling in pediatric and young adult cancers Journal Article

Authors:	Shukla, N.; Levine, M. F.; Gundem, G.; Domenico, D.; Spitzer, B.; Bouvier, N.; Arango-Ossa, J. E.; Glodzik, D.; Medina-Martínez, J. S.; Bhanot, U.; Gutiérrez-Abril, J.; Zhou, Y.; Fiala, E.; Stockfisch, E.; Li, S.; Rodriguez-Sanchez, M. I.; O'Donohue, T.; Cobbs, C.; Roehrl, M. H. A.; Benhamida, J.; Iglesias Cardenas, F.; Ortiz, M.; Kinnaman, M.; Roberts, S.; Ladanyi, M.; Modak, S.; Farouk-Sait, S.; Slotkin, E.; Karajannis, M. A.; Dela Cruz, F.; Glade Bender, J.; Zehir, A.; Viale, A.; Walsh, M. F.; Kung, A. L.; Papaemmanuil, E.
Article Title:	Feasibility of whole genome and transcriptome profiling in pediatric and young adult cancers
Abstract:	The utility of cancer whole genome and transcriptome sequencing (cWGTS) in oncology is increasingly recognized. However, implementation of cWGTS is challenged by the need to deliver results within clinically relevant timeframes, concerns about assay sensitivity, reporting and prioritization of findings. In a prospective research study we develop a workflow that reports comprehensive cWGTS results in 9 days. Comparison of cWGTS to diagnostic panel assays demonstrates the potential of cWGTS to capture all clinically reported mutations with comparable sensitivity in a single workflow. Benchmarking identifies a minimum of 80x as optimal depth for clinical WGS sequencing. Integration of germline, somatic DNA and RNA-seq data enable data-driven variant prioritization and reporting, with oncogenic findings reported in 54% more patients than standard of care. These results establish key technical considerations for the implementation of cWGTS as an integrated test in clinical oncology. Cancer whole-genome and transcriptome sequencing (cWGTS) has been challenging to implement in clinical settings. Here, the authors develop a workflow to deliver robust cWGTS analyses and reports within clinically-relevant timeframes for paediatric, adolescent and young adult solid tumour patients.
Keywords:	genetics; classification; neuroblastoma; validation; mutations; heterogeneity; variants; landscape; telomere length; annotation
Journal Title:	Nature Communications
Volume:	13
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2022-05-18
Start Page:	2485
Language:	English
ACCESSION:	WOS:000798996800017
DOI:	10.1038/s41467-022-30233-7
PROVIDER:	wos
PMCID:	PMC9117241
PUBMED:	35585047
Notes:	Article -- 2485 -- Source: Wos