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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
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.
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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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