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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6679157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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