: 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.

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. - In: DIAGNOSTICS. - ISSN 2075-4418. - 11:12(2021). [10.3390/diagnostics11122196]

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
Co-primo
;
Gelibter, Alain
Co-primo
;
Bottillo, Irene;Belardinilli, Francesca;Pisegna, Simona;De Renzi, Gianluigi;Marinelli, Daniele;Grammatico, Paola;Cortesi, Enrico;Giannini, Giuseppe
Penultimo
;
Gazzaniga, Paola
Ultimo
2021

Abstract

: 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.
KRAS G12C; circulating tumor DNA; clonal evolution; liquid biopsy; non-small-cell lung cancer
01 Pubblicazione su rivista::01a Articolo in rivista
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. - In: DIAGNOSTICS. - ISSN 2075-4418. - 11:12(2021). [10.3390/diagnostics11122196]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1601270
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