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Detection of BRAFV600E in Liquid Biopsy from Patients with Papillary Thyroid Cancer Is Associated with Tumor Aggressiveness and Response to Therapy

The detection of rare mutational targets in plasma (liquid biopsy) has emerged as a promising tool for the assessment of patients with cancer. We determined the presence of cell-free DNA containing the BRAFV600E mutations (cfBRAFV600E) in plasma samples from 57 patients with papillary thyroid cancer...

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Autores principales: Jensen, Kirk, Thakur, Shilpa, Patel, Aneeta, Mendonca-Torres, Maria Cecilia, Costello, John, Gomes-Lima, Cristiane Jeyce, Walter, Mary, Wartofsky, Leonard, Burman, Kenneth Dale, Bikas, Athanasios, Ylli, Dorina, Vasko, Vasyl V., Klubo-Gwiezdzinska, Joanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464493/
https://www.ncbi.nlm.nih.gov/pubmed/32748840
http://dx.doi.org/10.3390/jcm9082481
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author Jensen, Kirk
Thakur, Shilpa
Patel, Aneeta
Mendonca-Torres, Maria Cecilia
Costello, John
Gomes-Lima, Cristiane Jeyce
Walter, Mary
Wartofsky, Leonard
Burman, Kenneth Dale
Bikas, Athanasios
Ylli, Dorina
Vasko, Vasyl V.
Klubo-Gwiezdzinska, Joanna
author_facet Jensen, Kirk
Thakur, Shilpa
Patel, Aneeta
Mendonca-Torres, Maria Cecilia
Costello, John
Gomes-Lima, Cristiane Jeyce
Walter, Mary
Wartofsky, Leonard
Burman, Kenneth Dale
Bikas, Athanasios
Ylli, Dorina
Vasko, Vasyl V.
Klubo-Gwiezdzinska, Joanna
author_sort Jensen, Kirk
collection PubMed
description The detection of rare mutational targets in plasma (liquid biopsy) has emerged as a promising tool for the assessment of patients with cancer. We determined the presence of cell-free DNA containing the BRAFV600E mutations (cfBRAFV600E) in plasma samples from 57 patients with papillary thyroid cancer (PTC) with somatic BRAFV600E mutation-positive primary tumors using microfluidic digital PCR, and co-amplification at lower denaturation temperature (COLD) PCR. Mutant cfBRAFV600E alleles were detected in 24/57 (42.1%) of the examined patients. The presence of cfBRAFV600E was significantly associated with tumor size (p = 0.03), multifocal patterns of growth (p = 0.03), the presence of extrathyroidal gross extension (p = 0.02) and the presence of pulmonary micrometastases (p = 0.04). In patients with low-, intermediate- and high-risk PTCs, cfBRAFV600E was detected in 4/19 (21.0%), 8/22 (36.3%) and 12/16 (75.0%) of cases, respectively. Patients with detectable cfBRAFV600E were characterized by a 4.68 times higher likelihood of non-excellent response to therapy, as compared to patients without detectable cfBRAFV600E (OR (odds ratios), 4.68; 95% CI (confidence intervals)) 1.26–17.32; p = 0.02). In summary, the combination of digital polymerase chain reaction (dPCR) with COLD-PCR enables the detection of BRAFV600E in the liquid biopsy from patients with PTCs and could prove useful for the identification of patients with PTC at an increased risk for a structurally or biochemically incomplete or indeterminate response to treatment.
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spelling pubmed-74644932020-09-04 Detection of BRAFV600E in Liquid Biopsy from Patients with Papillary Thyroid Cancer Is Associated with Tumor Aggressiveness and Response to Therapy Jensen, Kirk Thakur, Shilpa Patel, Aneeta Mendonca-Torres, Maria Cecilia Costello, John Gomes-Lima, Cristiane Jeyce Walter, Mary Wartofsky, Leonard Burman, Kenneth Dale Bikas, Athanasios Ylli, Dorina Vasko, Vasyl V. Klubo-Gwiezdzinska, Joanna J Clin Med Article The detection of rare mutational targets in plasma (liquid biopsy) has emerged as a promising tool for the assessment of patients with cancer. We determined the presence of cell-free DNA containing the BRAFV600E mutations (cfBRAFV600E) in plasma samples from 57 patients with papillary thyroid cancer (PTC) with somatic BRAFV600E mutation-positive primary tumors using microfluidic digital PCR, and co-amplification at lower denaturation temperature (COLD) PCR. Mutant cfBRAFV600E alleles were detected in 24/57 (42.1%) of the examined patients. The presence of cfBRAFV600E was significantly associated with tumor size (p = 0.03), multifocal patterns of growth (p = 0.03), the presence of extrathyroidal gross extension (p = 0.02) and the presence of pulmonary micrometastases (p = 0.04). In patients with low-, intermediate- and high-risk PTCs, cfBRAFV600E was detected in 4/19 (21.0%), 8/22 (36.3%) and 12/16 (75.0%) of cases, respectively. Patients with detectable cfBRAFV600E were characterized by a 4.68 times higher likelihood of non-excellent response to therapy, as compared to patients without detectable cfBRAFV600E (OR (odds ratios), 4.68; 95% CI (confidence intervals)) 1.26–17.32; p = 0.02). In summary, the combination of digital polymerase chain reaction (dPCR) with COLD-PCR enables the detection of BRAFV600E in the liquid biopsy from patients with PTCs and could prove useful for the identification of patients with PTC at an increased risk for a structurally or biochemically incomplete or indeterminate response to treatment. MDPI 2020-08-02 /pmc/articles/PMC7464493/ /pubmed/32748840 http://dx.doi.org/10.3390/jcm9082481 Text en © 2020 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
Jensen, Kirk
Thakur, Shilpa
Patel, Aneeta
Mendonca-Torres, Maria Cecilia
Costello, John
Gomes-Lima, Cristiane Jeyce
Walter, Mary
Wartofsky, Leonard
Burman, Kenneth Dale
Bikas, Athanasios
Ylli, Dorina
Vasko, Vasyl V.
Klubo-Gwiezdzinska, Joanna
Detection of BRAFV600E in Liquid Biopsy from Patients with Papillary Thyroid Cancer Is Associated with Tumor Aggressiveness and Response to Therapy
title Detection of BRAFV600E in Liquid Biopsy from Patients with Papillary Thyroid Cancer Is Associated with Tumor Aggressiveness and Response to Therapy
title_full Detection of BRAFV600E in Liquid Biopsy from Patients with Papillary Thyroid Cancer Is Associated with Tumor Aggressiveness and Response to Therapy
title_fullStr Detection of BRAFV600E in Liquid Biopsy from Patients with Papillary Thyroid Cancer Is Associated with Tumor Aggressiveness and Response to Therapy
title_full_unstemmed Detection of BRAFV600E in Liquid Biopsy from Patients with Papillary Thyroid Cancer Is Associated with Tumor Aggressiveness and Response to Therapy
title_short Detection of BRAFV600E in Liquid Biopsy from Patients with Papillary Thyroid Cancer Is Associated with Tumor Aggressiveness and Response to Therapy
title_sort detection of brafv600e in liquid biopsy from patients with papillary thyroid cancer is associated with tumor aggressiveness and response to therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464493/
https://www.ncbi.nlm.nih.gov/pubmed/32748840
http://dx.doi.org/10.3390/jcm9082481
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