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BRAF Mutation Status in Circulating Tumor DNA from Patients with Metastatic Colorectal Cancer: Extended Mutation Analysis from the AGEO RASANC Study

In patients with metastatic colorectal cancer (mCRC), RAS and BRAF mutations are currently determined by tumor sample analysis. Here, we report BRAF mutation status analysis in paired tumor tissue and plasma samples of mCRC patients included in the AGEO RASANC prospective cohort study. Four hundred...

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Autores principales: Mas, Leo, Bachet, Jean-Baptiste, Taly, Valerie, Bouché, Olivier, Taieb, Julien, Cohen, Romain, Meurisse, Aurelia, Normand, Corinne, Gornet, Jean-Marc, Artru, Pascal, Louafi, Samy, Thirot-Bidault, Anne, Baumgaertner, Isabelle, Coriat, Romain, Tougeron, David, Lecomte, Thierry, Mary, Florence, Aparicio, Thomas, Marthey, Lysiane, Blons, Helene, Vernerey, Dewi, Laurent-Puig, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679157/
https://www.ncbi.nlm.nih.gov/pubmed/31319569
http://dx.doi.org/10.3390/cancers11070998
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author Mas, Leo
Bachet, Jean-Baptiste
Taly, Valerie
Bouché, Olivier
Taieb, Julien
Cohen, Romain
Meurisse, Aurelia
Normand, Corinne
Gornet, Jean-Marc
Artru, Pascal
Louafi, Samy
Thirot-Bidault, Anne
Baumgaertner, Isabelle
Coriat, Romain
Tougeron, David
Lecomte, Thierry
Mary, Florence
Aparicio, Thomas
Marthey, Lysiane
Blons, Helene
Vernerey, Dewi
Laurent-Puig, Pierre
author_facet Mas, Leo
Bachet, Jean-Baptiste
Taly, Valerie
Bouché, Olivier
Taieb, Julien
Cohen, Romain
Meurisse, Aurelia
Normand, Corinne
Gornet, Jean-Marc
Artru, Pascal
Louafi, Samy
Thirot-Bidault, Anne
Baumgaertner, Isabelle
Coriat, Romain
Tougeron, David
Lecomte, Thierry
Mary, Florence
Aparicio, Thomas
Marthey, Lysiane
Blons, Helene
Vernerey, Dewi
Laurent-Puig, Pierre
author_sort Mas, Leo
collection PubMed
description In patients with metastatic colorectal cancer (mCRC), RAS and BRAF mutations are currently determined by tumor sample analysis. Here, we report BRAF mutation status analysis in paired tumor tissue and plasma samples of mCRC patients included in the AGEO RASANC prospective cohort study. Four hundred and twenty-five patients were enrolled. Plasma samples were analyzed by next-generation sequencing (NGS). When no mutation was identified, we used two methylated specific biomarkers (digital droplet PCR) to determine the presence or absence of circulating tumor DNA (ctDNA). Patients with conclusive ctDNA results were defined as those with at least one mutation or one methylated biomarker. The kappa coefficient and accuracy were 0.79 (95% CI: 0.67–0.91) and 97.3% (95% CI: 95.2–98.6%) between the BRAF status in plasma and tissue for patients with available paired samples (n = 405), and 0.89 (95% CI: 0.80–0.99) and 98.5% (95% CI: 96.4–99.5%) for those with conclusive ctDNA (n = 323). The absence of liver metastasis was the main factor associated to inconclusive ctDNA results. In patients with liver metastasis, the kappa coefficient was 0.91 (95% CI, 0.81–1.00) and accuracy was 98.6% (95% CI, 96.5–99.6%). We demonstrate satisfying concordance between tissue and plasma BRAF mutation detection, especially in patients with liver metastasis, arguing for plasma ctDNA testing for routine BRAF mutation analysis in these patients.
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spelling pubmed-66791572019-08-19 BRAF Mutation Status in Circulating Tumor DNA from Patients with Metastatic Colorectal Cancer: Extended Mutation Analysis from the AGEO RASANC Study Mas, Leo Bachet, Jean-Baptiste Taly, Valerie Bouché, Olivier Taieb, Julien Cohen, Romain Meurisse, Aurelia Normand, Corinne Gornet, Jean-Marc Artru, Pascal Louafi, Samy Thirot-Bidault, Anne Baumgaertner, Isabelle Coriat, Romain Tougeron, David Lecomte, Thierry Mary, Florence Aparicio, Thomas Marthey, Lysiane Blons, Helene Vernerey, Dewi Laurent-Puig, Pierre Cancers (Basel) Article In patients with metastatic colorectal cancer (mCRC), RAS and BRAF mutations are currently determined by tumor sample analysis. Here, we report BRAF mutation status analysis in paired tumor tissue and plasma samples of mCRC patients included in the AGEO RASANC prospective cohort study. Four hundred and twenty-five patients were enrolled. Plasma samples were analyzed by next-generation sequencing (NGS). When no mutation was identified, we used two methylated specific biomarkers (digital droplet PCR) to determine the presence or absence of circulating tumor DNA (ctDNA). Patients with conclusive ctDNA results were defined as those with at least one mutation or one methylated biomarker. The kappa coefficient and accuracy were 0.79 (95% CI: 0.67–0.91) and 97.3% (95% CI: 95.2–98.6%) between the BRAF status in plasma and tissue for patients with available paired samples (n = 405), and 0.89 (95% CI: 0.80–0.99) and 98.5% (95% CI: 96.4–99.5%) for those with conclusive ctDNA (n = 323). The absence of liver metastasis was the main factor associated to inconclusive ctDNA results. In patients with liver metastasis, the kappa coefficient was 0.91 (95% CI, 0.81–1.00) and accuracy was 98.6% (95% CI, 96.5–99.6%). We demonstrate satisfying concordance between tissue and plasma BRAF mutation detection, especially in patients with liver metastasis, arguing for plasma ctDNA testing for routine BRAF mutation analysis in these patients. MDPI 2019-07-17 /pmc/articles/PMC6679157/ /pubmed/31319569 http://dx.doi.org/10.3390/cancers11070998 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mas, Leo
Bachet, Jean-Baptiste
Taly, Valerie
Bouché, Olivier
Taieb, Julien
Cohen, Romain
Meurisse, Aurelia
Normand, Corinne
Gornet, Jean-Marc
Artru, Pascal
Louafi, Samy
Thirot-Bidault, Anne
Baumgaertner, Isabelle
Coriat, Romain
Tougeron, David
Lecomte, Thierry
Mary, Florence
Aparicio, Thomas
Marthey, Lysiane
Blons, Helene
Vernerey, Dewi
Laurent-Puig, Pierre
BRAF Mutation Status in Circulating Tumor DNA from Patients with Metastatic Colorectal Cancer: Extended Mutation Analysis from the AGEO RASANC Study
title BRAF Mutation Status in Circulating Tumor DNA from Patients with Metastatic Colorectal Cancer: Extended Mutation Analysis from the AGEO RASANC Study
title_full BRAF Mutation Status in Circulating Tumor DNA from Patients with Metastatic Colorectal Cancer: Extended Mutation Analysis from the AGEO RASANC Study
title_fullStr BRAF Mutation Status in Circulating Tumor DNA from Patients with Metastatic Colorectal Cancer: Extended Mutation Analysis from the AGEO RASANC Study
title_full_unstemmed BRAF Mutation Status in Circulating Tumor DNA from Patients with Metastatic Colorectal Cancer: Extended Mutation Analysis from the AGEO RASANC Study
title_short BRAF Mutation Status in Circulating Tumor DNA from Patients with Metastatic Colorectal Cancer: Extended Mutation Analysis from the AGEO RASANC Study
title_sort braf mutation status in circulating tumor dna from patients with metastatic colorectal cancer: extended mutation analysis from the ageo rasanc study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679157/
https://www.ncbi.nlm.nih.gov/pubmed/31319569
http://dx.doi.org/10.3390/cancers11070998
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