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Comparison of Two Blood-Based Genotyping Tests to Investigate the KRAS G12C Mutation in Patients with Non-Small-Cell Lung Cancer at Failure of First-Line Treatments

Although molecular profiling at diagnosis has traditionally relied on direct sampling of neoplastic tissue, cancer clonal evolution represents a critical obstacle to use primary tissue biopsies to guide clinical decision-making at the time of progressive disease. Liquid biopsies might offer enormous...

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Autores principales: Nicolazzo, Chiara, Gelibter, Alain, Bottillo, Irene, Belardinilli, Francesca, Pisegna, Simona, De Renzi, Gianluigi, Marinelli, Daniele, Grammatico, Paola, Cortesi, Enrico, Giannini, Giuseppe, Gazzaniga, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700393/
https://www.ncbi.nlm.nih.gov/pubmed/34943432
http://dx.doi.org/10.3390/diagnostics11122196
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author Nicolazzo, Chiara
Gelibter, Alain
Bottillo, Irene
Belardinilli, Francesca
Pisegna, Simona
De Renzi, Gianluigi
Marinelli, Daniele
Grammatico, Paola
Cortesi, Enrico
Giannini, Giuseppe
Gazzaniga, Paola
author_facet Nicolazzo, Chiara
Gelibter, Alain
Bottillo, Irene
Belardinilli, Francesca
Pisegna, Simona
De Renzi, Gianluigi
Marinelli, Daniele
Grammatico, Paola
Cortesi, Enrico
Giannini, Giuseppe
Gazzaniga, Paola
author_sort Nicolazzo, Chiara
collection PubMed
description Although molecular profiling at diagnosis has traditionally relied on direct sampling of neoplastic tissue, cancer clonal evolution represents a critical obstacle to use primary tissue biopsies to guide clinical decision-making at the time of progressive disease. Liquid biopsies might offer enormous advantages over tissue biopsies, tracking in real-time temporal-based tumor dynamics following each line of treatment. Here, we compared two liquid biopsy assays, specifically real-time polymerase chain reaction and next-generation sequencing, to track the KRAS G12C mutation at onset of progression from previous lines of therapy. The KRAS G12C mutation was acquired at the time of progressive disease in 24% of patients. Furthermore, all patients with KRAS G12C mutation-positive tissue became negative in ctDNA at progressive disease. The presence of other somatic mutations in all these samples confirmed the tumor origin of the circulating DNA. This pilot study suggests that in the assessment of the plasma KRAS G12C mutation as a druggable target, real-time PCR assay Idylla might be a suitable approach to better match patients to interventional biomarker-targeted therapies.
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spelling pubmed-87003932021-12-24 Comparison of Two Blood-Based Genotyping Tests to Investigate the KRAS G12C Mutation in Patients with Non-Small-Cell Lung Cancer at Failure of First-Line Treatments Nicolazzo, Chiara Gelibter, Alain Bottillo, Irene Belardinilli, Francesca Pisegna, Simona De Renzi, Gianluigi Marinelli, Daniele Grammatico, Paola Cortesi, Enrico Giannini, Giuseppe Gazzaniga, Paola Diagnostics (Basel) Communication Although molecular profiling at diagnosis has traditionally relied on direct sampling of neoplastic tissue, cancer clonal evolution represents a critical obstacle to use primary tissue biopsies to guide clinical decision-making at the time of progressive disease. Liquid biopsies might offer enormous advantages over tissue biopsies, tracking in real-time temporal-based tumor dynamics following each line of treatment. Here, we compared two liquid biopsy assays, specifically real-time polymerase chain reaction and next-generation sequencing, to track the KRAS G12C mutation at onset of progression from previous lines of therapy. The KRAS G12C mutation was acquired at the time of progressive disease in 24% of patients. Furthermore, all patients with KRAS G12C mutation-positive tissue became negative in ctDNA at progressive disease. The presence of other somatic mutations in all these samples confirmed the tumor origin of the circulating DNA. This pilot study suggests that in the assessment of the plasma KRAS G12C mutation as a druggable target, real-time PCR assay Idylla might be a suitable approach to better match patients to interventional biomarker-targeted therapies. MDPI 2021-11-25 /pmc/articles/PMC8700393/ /pubmed/34943432 http://dx.doi.org/10.3390/diagnostics11122196 Text en © 2021 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
Nicolazzo, Chiara
Gelibter, Alain
Bottillo, Irene
Belardinilli, Francesca
Pisegna, Simona
De Renzi, Gianluigi
Marinelli, Daniele
Grammatico, Paola
Cortesi, Enrico
Giannini, Giuseppe
Gazzaniga, Paola
Comparison of Two Blood-Based Genotyping Tests to Investigate the KRAS G12C Mutation in Patients with Non-Small-Cell Lung Cancer at Failure of First-Line Treatments
title Comparison of Two Blood-Based Genotyping Tests to Investigate the KRAS G12C Mutation in Patients with Non-Small-Cell Lung Cancer at Failure of First-Line Treatments
title_full Comparison of Two Blood-Based Genotyping Tests to Investigate the KRAS G12C Mutation in Patients with Non-Small-Cell Lung Cancer at Failure of First-Line Treatments
title_fullStr Comparison of Two Blood-Based Genotyping Tests to Investigate the KRAS G12C Mutation in Patients with Non-Small-Cell Lung Cancer at Failure of First-Line Treatments
title_full_unstemmed Comparison of Two Blood-Based Genotyping Tests to Investigate the KRAS G12C Mutation in Patients with Non-Small-Cell Lung Cancer at Failure of First-Line Treatments
title_short Comparison of Two Blood-Based Genotyping Tests to Investigate the KRAS G12C Mutation in Patients with Non-Small-Cell Lung Cancer at Failure of First-Line Treatments
title_sort comparison of two blood-based genotyping tests to investigate the kras g12c mutation in patients with non-small-cell lung cancer at failure of first-line treatments
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700393/
https://www.ncbi.nlm.nih.gov/pubmed/34943432
http://dx.doi.org/10.3390/diagnostics11122196
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