Development and validation of a multigene variant profiling assay to guide targeted and immuno therapy selection in solid tumors

We present data on analytical validation of the multigene variant profiling assay (CellDx) to provide actionable indications for selection of targeted and immune checkpoint inhibitor (ICI) therapy in solid tumors. CellDx includes Next Generation Sequencing (NGS) profiling of gene variants in a targe...

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Bibliographic Details
Published in:	PloS one Vol. 16; no. 2; p. e0246048
Main Authors:	Akolkar, Dadasaheb, Patil, Darshana, Srivastava, Navin, Patil, Revati, Datta, Vineet, Apurwa, Sachin, Yashwante, Nitin, Dhasarathan, Raja, Gosavi, Rahul, John, Jinumary, Khan, Shabishta, Jadhav, Ninad, Mene, Priti, Ahire, Dhanashri, Pawar, Sushant, Bodke, Harshal, Sahoo, Subhraline, Nile, Arun, Saindane, Dinesh, Darokar, Harshal, Devhare, Pradip, Srinivasan, Ajay, Datar, Rajan
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 08-02-2021 Public Library of Science (PLoS)
Subjects:	Abnormalities Amplification Aneuploidy Biochemical assays Biology and Life Sciences Cancer Capillary electrophoresis Carcinogenesis Carcinogens Data analysis Deoxyribonucleic acid DNA DNA sequencing Drug therapy Editing Electrophoresis Epidermal growth factor Epidermal growth factor receptors Ethics FDA approval Gene fusion Genes Genetic aspects Genetic variation Genetics Genomics Growth factors Immune checkpoint inhibitors Immunotherapy Kinases Lung cancer Lung diseases Medical research Medicine and Health Sciences Methodology Methods Microsatellite instability Mismatch repair MLH1 protein Molecular targeted therapy Monoclonal antibodies MSH2 protein MSH6 protein Mutation Nucleotide sequencing Oncology, Experimental Paraffin Paraffins Patients PD-L1 protein Pembrolizumab Protein-tyrosine kinase Research and analysis methods Reviews Ribonucleic acid RNA Software Solid tumors Targeted cancer therapy Tumors Tyrosine Visualization India United States > US
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Summary:	We present data on analytical validation of the multigene variant profiling assay (CellDx) to provide actionable indications for selection of targeted and immune checkpoint inhibitor (ICI) therapy in solid tumors. CellDx includes Next Generation Sequencing (NGS) profiling of gene variants in a targeted 452-gene panel as well as status of total Tumor Mutation Burden (TMB), Microsatellite instability (MSI), Mismatch Repair (MMR) and Programmed Cell Death-Ligand 1 (PD-L1) respectively. Validation parameters included accuracy, sensitivity, specificity and reproducibility for detection of Single Nucleotide Alterations (SNAs), Copy Number Alterations (CNAs), Insertions and Deletions (Indels), Gene fusions, MSI and PDL1. Cumulative analytical sensitivity and specificity of the assay were 99.03 (95% CI: 96.54-99.88) and 99.23% (95% CI: 98.54% - 99.65%) respectively with 99.20% overall Accuracy (95% CI: 98.57% - 99.60%) and 99.7% Precision based on evaluation of 116 reference samples. The clinical performance of CellDx was evaluated in a subsequent analysis of 299 clinical samples where 861 unique mutations were detected of which 791 were oncogenic and 47 were actionable. Indications in MMR, MSI and TMB for selection of ICI therapies were also detected in the clinical samples. The high specificity, sensitivity, accuracy and reproducibility of the CellDx assay is suitable for clinical application for guiding selection of targeted and immunotherapy agents in patients with solid organ tumors.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: All author except RD2 are employees of the Funding Institution, i.e., Datar Cancer Genetics (DCG), which offers commercial services in oncology. RD2 is the founder and Managing Director of the Funding Institution, and holds patents on products in development as well as marketed products which incorporate technology described in this manuscript as well as other similar technologies. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0246048