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
Chiara Nicolazzo,
Alain Gelibter,
Irene Bottillo,
Francesca Belardinilli,
Simona Pisegna,
Gianluigi De Renzi,
Daniele Marinelli,
Paola Grammatico,
Enrico Cortesi,
Giuseppe Giannini,
Paola Gazzaniga
Affiliations
Chiara Nicolazzo
Cancer Liquid Biopsy Unit, Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy
Alain Gelibter
Department of Radiology, Oncology and Pathology, Sapienza University of Rome, 00161 Rome, Italy
Irene Bottillo
Laboratory of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, 00152 Rome, Italy
Francesca Belardinilli
Laboratory of Molecular Oncology, Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy
Simona Pisegna
Department of Radiology, Oncology and Pathology, Sapienza University of Rome, 00161 Rome, Italy
Gianluigi De Renzi
Cancer Liquid Biopsy Unit, Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy
Daniele Marinelli
Department of Radiology, Oncology and Pathology, Sapienza University of Rome, 00161 Rome, Italy
Paola Grammatico
Laboratory of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, 00152 Rome, Italy
Enrico Cortesi
Department of Radiology, Oncology and Pathology, Sapienza University of Rome, 00161 Rome, Italy
Giuseppe Giannini
Laboratory of Molecular Oncology, Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy
Paola Gazzaniga
Cancer Liquid Biopsy Unit, Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy
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.
