Development and Clinical Utility of a Blood-Based Test Service for the Rapid Identification of Actionable Mutations in Non–Small Cell Lung Carcinoma
| Autor: | Ubaradka G. Sathyanarayana, Kristina Koch, Hestia Mellert, Samantha Cooper, Trudi Foreman, Paula Stonemetz, Scott Thurston, Westen Hahn, Jakkie Greer, Dawne N. Shelton, Dianna Maar, Leisa Jackson, Nicholas F. Dupuis, Gary Pestano, Amanda Weaver |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Lung Neoplasms Oncogene Proteins Fusion DNA Mutational Analysis Cell Cycle Proteins Bioinformatics medicine.disease_cause Pathology and Forensic Medicine Proto-Oncogene Proteins p21(ras) 03 medical and health sciences Exon T790M 0302 clinical medicine Carcinoma Non-Small-Cell Lung Internal medicine medicine Carcinoma Humans Anaplastic lymphoma kinase Anaplastic Lymphoma Kinase Gene Mutation business.industry Serine Endopeptidases Receptor Protein-Tyrosine Kinases Cancer Exons medicine.disease ErbB Receptors 030104 developmental biology 030220 oncology & carcinogenesis Molecular Medicine KRAS business Microtubule-Associated Proteins |
| Zdroj: | The Journal of Molecular Diagnostics. 19:404-416 |
| ISSN: | 1525-1578 |
| DOI: | 10.1016/j.jmoldx.2016.11.004 |
| Popis: | Nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder the ability to pursue optimal treatment strategies. This study validates a blood-based genome-testing service that provides accurate results within 72 hours. We focused on targetable variants in advanced non-small cell lung carcinoma-epidermal growth factor receptor gene (EGFR) variant L858R, exon 19 deletion (ΔE746-A750), and T790M; GTPase Kirsten ras gene (KRAS) variants G12C/D/V; and echinoderm microtubule associated protein like and 4 anaplastic lymphoma receptor tyrosine kinase fusion (EML4-ALK) transcripts 1/2/3. Test development included method and clinical validation using samples from donors with (n = 219) or without (n = 30) cancer. Clinical sensitivity and specificity for each variant ranged from 78.6% to 100% and 94.2% to 100%, respectively. We also report on 1643 non-small cell lung carcinoma samples processed in our CLIA-certified laboratory. Mutation results were available within 72 hours for 94% of the tests evaluated. We detected 10.5% mutations for EGFR sensitizing (n = 2801 samples tested), 13.8% mutations for EGFR resistance (n = 1055), 13.2% mutations in KRAS (n = 3477), and 2% mutations for EML4-ALK fusion (n = 304). This rapid, highly sensitive, and actionable blood-based assay service expands testing options and supports faster treatment decisions. |
| Databáze: | OpenAIRE |
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