Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer

Vidya H Veldore,1,* Anuradha Choughule,2,* Tejaswi Routhu,1 Nitin Mandloi,1 Vanita Noronha,2 Amit Joshi,2 Amit Dutt,3 Ravi Gupta,1 Ramprasad Vedam,1 Kumar Prabhash2 1MedGenome Labs Private Ltd,, Bangalore, India; 2Tata Memorial Centre, Parel, Mumbai, India; 3The Advanced Centre for Treatment, Resear...

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Autores principales:	Veldore VH, Choughule A, Routhu T, Mandloi N, Noronha V, Joshi A, Dutt A, Gupta R, Vedam R, Prabhash K
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Liquid Biopsy NSCLC EGFR ctDNA NGS Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/75a83c5f0528444c8a9f3e281fae022b
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spelling	oai:doaj.org-article:75a83c5f0528444c8a9f3e281fae022b2021-12-02T01:51:08ZValidation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer1179-2728https://doaj.org/article/75a83c5f0528444c8a9f3e281fae022b2018-01-01T00:00:00Zhttps://www.dovepress.com/validation-of-liquid-biopsy-plasma-cell-free-dna-testing-in-clinical-m-peer-reviewed-article-LCTThttps://doaj.org/toc/1179-2728Vidya H Veldore,1,* Anuradha Choughule,2,* Tejaswi Routhu,1 Nitin Mandloi,1 Vanita Noronha,2 Amit Joshi,2 Amit Dutt,3 Ravi Gupta,1 Ramprasad Vedam,1 Kumar Prabhash2 1MedGenome Labs Private Ltd,, Bangalore, India; 2Tata Memorial Centre, Parel, Mumbai, India; 3The Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Kharghar, Navi Mumbai, Maharashtra, India *These authors contributed equally to this work Abstract: Plasma cell-free tumor DNA, or circulating tumor DNA (ctDNA), from liquid biopsy is a potential source of tumor genetic material, in the absence of tissue biopsy, for EGFR testing. Our validation study reiterates the clinical utility of ctDNA next generation sequencing (NGS) for EGFR mutation testing in non-small cell lung cancer (NSCLC). A total of 163 NSCLC cases were included in the validation, of which 132 patients had paired tissue biopsy and ctDNA. We chose to validate ctDNA using deep sequencing with custom designed bioinformatics methods that could detect somatic mutations at allele frequencies as low as 0.01%. Benchmarking allele specific real time PCR as one of the standard methods for tissue-based EGFR mutation testing, the ctDNA NGS test was validated on all the plasma derived cell-free DNA samples. We observed a high concordance (96.96%) between tissue biopsy and ctDNA for oncogenic driver mutations in Exon 19 and Exon 21 of the EGFR gene. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the assay were 91.1%, 100% 100%, 95.6%, and 97%, respectively. A false negative rate of 3% was observed. A subset of mutations was also verified on droplet digital PCR. Sixteen percent EGFR mutation positivity was observed in patients where only liquid biopsy was available, thus creating options for targeted therapy. This is the first and largest study from India, demonstrating successful validation of circulating cell-free DNA as a clinically useful material for molecular testing in NSCLC. Keywords: liquid biopsy, NSCLC, EGFR, ctDNA, NGSVeldore VHChoughule ARouthu TMandloi NNoronha VJoshi ADutt AGupta RVedam RPrabhash KDove Medical PressarticleLiquid BiopsyNSCLCEGFRctDNANGSNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol Volume 9, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Liquid Biopsy NSCLC EGFR ctDNA NGS Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Liquid Biopsy NSCLC EGFR ctDNA NGS Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Veldore VH Choughule A Routhu T Mandloi N Noronha V Joshi A Dutt A Gupta R Vedam R Prabhash K Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer
description	Vidya H Veldore,1,* Anuradha Choughule,2,* Tejaswi Routhu,1 Nitin Mandloi,1 Vanita Noronha,2 Amit Joshi,2 Amit Dutt,3 Ravi Gupta,1 Ramprasad Vedam,1 Kumar Prabhash2 1MedGenome Labs Private Ltd,, Bangalore, India; 2Tata Memorial Centre, Parel, Mumbai, India; 3The Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Kharghar, Navi Mumbai, Maharashtra, India *These authors contributed equally to this work Abstract: Plasma cell-free tumor DNA, or circulating tumor DNA (ctDNA), from liquid biopsy is a potential source of tumor genetic material, in the absence of tissue biopsy, for EGFR testing. Our validation study reiterates the clinical utility of ctDNA next generation sequencing (NGS) for EGFR mutation testing in non-small cell lung cancer (NSCLC). A total of 163 NSCLC cases were included in the validation, of which 132 patients had paired tissue biopsy and ctDNA. We chose to validate ctDNA using deep sequencing with custom designed bioinformatics methods that could detect somatic mutations at allele frequencies as low as 0.01%. Benchmarking allele specific real time PCR as one of the standard methods for tissue-based EGFR mutation testing, the ctDNA NGS test was validated on all the plasma derived cell-free DNA samples. We observed a high concordance (96.96%) between tissue biopsy and ctDNA for oncogenic driver mutations in Exon 19 and Exon 21 of the EGFR gene. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the assay were 91.1%, 100% 100%, 95.6%, and 97%, respectively. A false negative rate of 3% was observed. A subset of mutations was also verified on droplet digital PCR. Sixteen percent EGFR mutation positivity was observed in patients where only liquid biopsy was available, thus creating options for targeted therapy. This is the first and largest study from India, demonstrating successful validation of circulating cell-free DNA as a clinically useful material for molecular testing in NSCLC. Keywords: liquid biopsy, NSCLC, EGFR, ctDNA, NGS
format	article
author	Veldore VH Choughule A Routhu T Mandloi N Noronha V Joshi A Dutt A Gupta R Vedam R Prabhash K
author_facet	Veldore VH Choughule A Routhu T Mandloi N Noronha V Joshi A Dutt A Gupta R Vedam R Prabhash K
author_sort	Veldore VH
title	Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer
title_short	Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer
title_full	Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer
title_fullStr	Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer
title_full_unstemmed	Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer
title_sort	validation of liquid biopsy: plasma cell-free dna testing in clinical management of advanced non-small cell lung cancer
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/75a83c5f0528444c8a9f3e281fae022b
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Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer

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