TY - JOUR
T1 - An Integrated Next-Generation Sequencing System for Analyzing DNA Mutations, Gene Fusions, and RNA Expression in Lung Cancer
AU - Haynes, Brian C.
AU - Blidner, Richard A.
AU - Cardwell, Robyn D.
AU - Zeigler, Robert
AU - Gokul, Shobha
AU - Thibert, Julie R.
AU - Chen, Liangjing
AU - Fujimoto, Junya
AU - Papadimitrakopoulou, Vassiliki A.
AU - Wistuba, Ignacio I.
AU - Latham, Gary J.
N1 - Funding Information:
Grant Support: This work was supported in part by Grant CP120017 from the Cancer Prevention and Research Institute of Texas to Asuragen (PI: G.J.L.), by the National Institute of Environmental Health Sciences of the National Institutes of Health under award number R43ES024365 (PI: B.C.H.), and by the National Institute of General Medical Sciences under award number R44GM111062 (PI: B.C.H.). The authors thank Annette Schlageter for assistance with the manuscript.
Publisher Copyright:
© 2019
PY - 2019/6
Y1 - 2019/6
N2 - We developed and characterized a next-generation sequencing (NGS) technology for streamlined analysis of DNA and RNA using low-input, low-quality cancer specimens. A single-workflow, targeted NGS panel for non–small cell lung cancer (NSCLC) was designed covering 135 RNA and 55 DNA disease-relevant targets. This multiomic panel was used to assess 219 formalin-fixed paraffin-embedded NSCLC surgical resections and core needle biopsies. Mutations and expression phenotypes were identified consistent with previous large-scale genomic studies, including mutually exclusive DNA and RNA oncogenic driver events. Evaluation of a second cohort of low cell count fine-needle aspirate smears from the BATTLE-2 trial yielded 97% agreement with an independent, validated NGS panel that was used with matched surgical specimens. Collectively, our data indicate that broad, clinically actionable insights that previously required independent assays, workflows, and analyses to assess both DNA and RNA can be conjoined in a first-tier, highly multiplexed NGS test, thereby providing faster, simpler, and more economical results.
AB - We developed and characterized a next-generation sequencing (NGS) technology for streamlined analysis of DNA and RNA using low-input, low-quality cancer specimens. A single-workflow, targeted NGS panel for non–small cell lung cancer (NSCLC) was designed covering 135 RNA and 55 DNA disease-relevant targets. This multiomic panel was used to assess 219 formalin-fixed paraffin-embedded NSCLC surgical resections and core needle biopsies. Mutations and expression phenotypes were identified consistent with previous large-scale genomic studies, including mutually exclusive DNA and RNA oncogenic driver events. Evaluation of a second cohort of low cell count fine-needle aspirate smears from the BATTLE-2 trial yielded 97% agreement with an independent, validated NGS panel that was used with matched surgical specimens. Collectively, our data indicate that broad, clinically actionable insights that previously required independent assays, workflows, and analyses to assess both DNA and RNA can be conjoined in a first-tier, highly multiplexed NGS test, thereby providing faster, simpler, and more economical results.
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U2 - 10.1016/j.tranon.2019.02.012
DO - 10.1016/j.tranon.2019.02.012
M3 - Article
C2 - 30981944
AN - SCOPUS:85064264645
SN - 1936-5233
VL - 12
SP - 836
EP - 845
JO - Translational Oncology
JF - Translational Oncology
IS - 6
ER -