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Limits and potential of targeted sequencing analysis of liquid biopsy in patients with lung and colon carcinoma
The circulating free tumor DNA (ctDNA) represents an alternative, minimally invasive source of tumor DNA for molecular profiling. Targeted sequencing with next generation sequencing (NGS) can assess hundred mutations starting from a low DNA input. We performed NGS analysis of ctDNA from 44 patients...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341823/ https://www.ncbi.nlm.nih.gov/pubmed/27448974 http://dx.doi.org/10.18632/oncotarget.10704 |
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author | Rachiglio, Anna Maria Abate, Riziero Esposito Sacco, Alessandra Pasquale, Raffaella Fenizia, Francesca Lambiase, Matilde Morabito, Alessandro Montanino, Agnese Rocco, Gaetano Romano, Carmen Nappi, Anna Iaffaioli, Rosario Vincenzo Tatangelo, Fabiana Botti, Gerardo Ciardiello, Fortunato Maiello, Monica R. De Luca, Antonella Normanno, Nicola |
author_facet | Rachiglio, Anna Maria Abate, Riziero Esposito Sacco, Alessandra Pasquale, Raffaella Fenizia, Francesca Lambiase, Matilde Morabito, Alessandro Montanino, Agnese Rocco, Gaetano Romano, Carmen Nappi, Anna Iaffaioli, Rosario Vincenzo Tatangelo, Fabiana Botti, Gerardo Ciardiello, Fortunato Maiello, Monica R. De Luca, Antonella Normanno, Nicola |
author_sort | Rachiglio, Anna Maria |
collection | PubMed |
description | The circulating free tumor DNA (ctDNA) represents an alternative, minimally invasive source of tumor DNA for molecular profiling. Targeted sequencing with next generation sequencing (NGS) can assess hundred mutations starting from a low DNA input. We performed NGS analysis of ctDNA from 44 patients with metastatic non-small-cell lung carcinoma (NSCLC) and 35 patients with metastatic colorectal carcinoma (CRC). NGS detected EGFR mutations in 17/22 plasma samples from EGFR-mutant NSCLC patients (sensitivity 77.3%). The concordance rate between tissue and plasma in NSCLC was much lower for other mutations such as KRAS that, based on the allelic frequency and the fraction of neoplastic cells, were likely to be sub-clonal. NGS also identified EGFR mutations in plasma samples from two patients with EGFR wild type tumor tissue. Both mutations were confirmed by droplet digital PCR (ddPCR) in both plasma and tissue samples. In CRC, the sensitivity of the NGS plasma analysis for RAS mutations was 100% (6/6) in patients that had not resection of the primary tumor before blood drawing, and 46.2% (6/13) in patients with primary tumor resected before enrollment. Our study showed that NGS is a suitable method for plasma testing. However, its clinical sensitivity is significantly affected by the presence of the primary tumor and by the heterogeneity of driver mutations. |
format | Online Article Text |
id | pubmed-5341823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53418232017-03-23 Limits and potential of targeted sequencing analysis of liquid biopsy in patients with lung and colon carcinoma Rachiglio, Anna Maria Abate, Riziero Esposito Sacco, Alessandra Pasquale, Raffaella Fenizia, Francesca Lambiase, Matilde Morabito, Alessandro Montanino, Agnese Rocco, Gaetano Romano, Carmen Nappi, Anna Iaffaioli, Rosario Vincenzo Tatangelo, Fabiana Botti, Gerardo Ciardiello, Fortunato Maiello, Monica R. De Luca, Antonella Normanno, Nicola Oncotarget Research Paper The circulating free tumor DNA (ctDNA) represents an alternative, minimally invasive source of tumor DNA for molecular profiling. Targeted sequencing with next generation sequencing (NGS) can assess hundred mutations starting from a low DNA input. We performed NGS analysis of ctDNA from 44 patients with metastatic non-small-cell lung carcinoma (NSCLC) and 35 patients with metastatic colorectal carcinoma (CRC). NGS detected EGFR mutations in 17/22 plasma samples from EGFR-mutant NSCLC patients (sensitivity 77.3%). The concordance rate between tissue and plasma in NSCLC was much lower for other mutations such as KRAS that, based on the allelic frequency and the fraction of neoplastic cells, were likely to be sub-clonal. NGS also identified EGFR mutations in plasma samples from two patients with EGFR wild type tumor tissue. Both mutations were confirmed by droplet digital PCR (ddPCR) in both plasma and tissue samples. In CRC, the sensitivity of the NGS plasma analysis for RAS mutations was 100% (6/6) in patients that had not resection of the primary tumor before blood drawing, and 46.2% (6/13) in patients with primary tumor resected before enrollment. Our study showed that NGS is a suitable method for plasma testing. However, its clinical sensitivity is significantly affected by the presence of the primary tumor and by the heterogeneity of driver mutations. Impact Journals LLC 2016-07-19 /pmc/articles/PMC5341823/ /pubmed/27448974 http://dx.doi.org/10.18632/oncotarget.10704 Text en Copyright: © 2016 Rachiglio et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Rachiglio, Anna Maria Abate, Riziero Esposito Sacco, Alessandra Pasquale, Raffaella Fenizia, Francesca Lambiase, Matilde Morabito, Alessandro Montanino, Agnese Rocco, Gaetano Romano, Carmen Nappi, Anna Iaffaioli, Rosario Vincenzo Tatangelo, Fabiana Botti, Gerardo Ciardiello, Fortunato Maiello, Monica R. De Luca, Antonella Normanno, Nicola Limits and potential of targeted sequencing analysis of liquid biopsy in patients with lung and colon carcinoma |
title | Limits and potential of targeted sequencing analysis of liquid biopsy in patients with lung and colon carcinoma |
title_full | Limits and potential of targeted sequencing analysis of liquid biopsy in patients with lung and colon carcinoma |
title_fullStr | Limits and potential of targeted sequencing analysis of liquid biopsy in patients with lung and colon carcinoma |
title_full_unstemmed | Limits and potential of targeted sequencing analysis of liquid biopsy in patients with lung and colon carcinoma |
title_short | Limits and potential of targeted sequencing analysis of liquid biopsy in patients with lung and colon carcinoma |
title_sort | limits and potential of targeted sequencing analysis of liquid biopsy in patients with lung and colon carcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341823/ https://www.ncbi.nlm.nih.gov/pubmed/27448974 http://dx.doi.org/10.18632/oncotarget.10704 |
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