1. Hybrid Capture–Based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Non–Small Cell Lung Cancer
- Author
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Brady Forcier, Alexa B. Schrock, Siraj M. Ali, Jon Chung, Allison Welsh, Jeffrey S. Ross, Philip J. Stephens, Dean Pavlick, Vincent A. Miller, Alice T. Shaw, Eric H. Bernicker, Sai-Hong Ignatius Ou, Tianhong Li, Benjamin C. Creelan, and Ibiayi Dagogo-Jack
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Genomic profiling ,business.industry ,medicine.medical_treatment ,Hybrid capture ,medicine.disease ,medicine.disease_cause ,Targeted therapy ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Circulating tumor DNA ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,KRAS ,Liquid biopsy ,business ,Lung cancer ,Gene - Abstract
Introduction Genomic profiling informs selection of matched targeted therapies as part of routine clinical care in NSCLC. Tissue biopsy is the criterion standard; however, genomic profiling of blood-derived circulating tumor DNA (ctDNA) has emerged as a minimally invasive alternative. Methods Hybrid capture–based genomic profiling of 62 genes was performed on blood-based ctDNA from 1552 patients with NSCLC. Results Evidence of ctDNA was detected in 80% of samples, and in 86% of these cases, at least one reportable genomic alteration (GA) was detected. Frequently altered genes were tumor protein p53 gene (TP53) (59%), EGFR (25%), and KRAS (17%). Comparative analysis with a tissue genomic database (N = 21,500) showed similar frequencies of GAs per gene, although KRAS mutation and EGFR T790M were more frequent in tissue and ctDNA, respectively (both p Conclusions Genomic profiling of ctDNA detected clinically relevant GAs in a significant subset of NSCLC cases. Most alterations detected in matched tissue were also detected in ctDNA. These results suggest the utility of ctDNA testing in advanced NSCLC as a complementary approach to tissue testing. Blood-based ctDNA testing may be particularly useful at the time of progression during targeted therapy.
- Published
- 2019
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