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Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival

Sporadic colorectal cancer (sCRC) initially presents as metastatic tumors in 25–30% of patients. The 5-year overall survival (OS) in patients with metastatic sCRC is 50%, falling to 10% in patients presenting with synchronous metastatic disease (stage IV). In this study, we systematically analyzed t...

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Autores principales: Sayagués, José María, Montero, Juan Carlos, Jiménez-Pérez, Andrea, del Carmen, Sofía, Rodríguez, Marta, Vidal Tocino, Rosario, Montero, Enrique, Sanz, Julia, Abad, Mar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10179090/
https://www.ncbi.nlm.nih.gov/pubmed/37176143
http://dx.doi.org/10.3390/ijms24098438
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author Sayagués, José María
Montero, Juan Carlos
Jiménez-Pérez, Andrea
del Carmen, Sofía
Rodríguez, Marta
Vidal Tocino, Rosario
Montero, Enrique
Sanz, Julia
Abad, Mar
author_facet Sayagués, José María
Montero, Juan Carlos
Jiménez-Pérez, Andrea
del Carmen, Sofía
Rodríguez, Marta
Vidal Tocino, Rosario
Montero, Enrique
Sanz, Julia
Abad, Mar
author_sort Sayagués, José María
collection PubMed
description Sporadic colorectal cancer (sCRC) initially presents as metastatic tumors in 25–30% of patients. The 5-year overall survival (OS) in patients with metastatic sCRC is 50%, falling to 10% in patients presenting with synchronous metastatic disease (stage IV). In this study, we systematically analyzed the mutations of RAS, PIK3CA and BRAF genes in circulating tumor DNA (ctDNA) and tumoral tissue DNA (ttDNA) from 51 synchronous metastatic colorectal carcinoma (SMCC) patients by real-time PCR, and their relationship with the clinical, biological and histological features of disease at diagnosis. The highest frequency of mutations detected was in the KRAS gene, in tumor biopsies and plasma samples, followed by mutations of the PIK3CA, NRAS and BRAF genes. Overall, plasma systematically contained those genetic abnormalities observed in the tumor biopsy sample from the same subject, the largest discrepancies detected between the tumor biopsy and plasma from the same patient being for mutations in the KRAS and PIK3CA genes, with concordances of genotyping results between ttDNA and ctDNA at diagnosis of 75% and 84%, respectively. Of the 51 SMCC patients in the study, 25 (49%) showed mutations in at least 1 of the 4 genes analyzed in patient plasma. From the prognostic point of view, the presence and number of the most common mutations in the RAS, PIK3CA and BRAF genes in plasma from SMCC patients are independent prognostic factors for OS. Determination of the mutational status of ctDNA in SMCC could be a key tool for the clinical management of patients.
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spelling pubmed-101790902023-05-13 Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival Sayagués, José María Montero, Juan Carlos Jiménez-Pérez, Andrea del Carmen, Sofía Rodríguez, Marta Vidal Tocino, Rosario Montero, Enrique Sanz, Julia Abad, Mar Int J Mol Sci Communication Sporadic colorectal cancer (sCRC) initially presents as metastatic tumors in 25–30% of patients. The 5-year overall survival (OS) in patients with metastatic sCRC is 50%, falling to 10% in patients presenting with synchronous metastatic disease (stage IV). In this study, we systematically analyzed the mutations of RAS, PIK3CA and BRAF genes in circulating tumor DNA (ctDNA) and tumoral tissue DNA (ttDNA) from 51 synchronous metastatic colorectal carcinoma (SMCC) patients by real-time PCR, and their relationship with the clinical, biological and histological features of disease at diagnosis. The highest frequency of mutations detected was in the KRAS gene, in tumor biopsies and plasma samples, followed by mutations of the PIK3CA, NRAS and BRAF genes. Overall, plasma systematically contained those genetic abnormalities observed in the tumor biopsy sample from the same subject, the largest discrepancies detected between the tumor biopsy and plasma from the same patient being for mutations in the KRAS and PIK3CA genes, with concordances of genotyping results between ttDNA and ctDNA at diagnosis of 75% and 84%, respectively. Of the 51 SMCC patients in the study, 25 (49%) showed mutations in at least 1 of the 4 genes analyzed in patient plasma. From the prognostic point of view, the presence and number of the most common mutations in the RAS, PIK3CA and BRAF genes in plasma from SMCC patients are independent prognostic factors for OS. Determination of the mutational status of ctDNA in SMCC could be a key tool for the clinical management of patients. MDPI 2023-05-08 /pmc/articles/PMC10179090/ /pubmed/37176143 http://dx.doi.org/10.3390/ijms24098438 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Sayagués, José María
Montero, Juan Carlos
Jiménez-Pérez, Andrea
del Carmen, Sofía
Rodríguez, Marta
Vidal Tocino, Rosario
Montero, Enrique
Sanz, Julia
Abad, Mar
Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival
title Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival
title_full Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival
title_fullStr Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival
title_full_unstemmed Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival
title_short Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival
title_sort analysis of circulating tumor dna in synchronous metastatic colorectal cancer at diagnosis predicts overall patient survival
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10179090/
https://www.ncbi.nlm.nih.gov/pubmed/37176143
http://dx.doi.org/10.3390/ijms24098438
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