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

Diagnostics

Gianluigi De Renzi¹  Chiara Nicolazzo¹  Paola Gazzaniga¹  Simona Pisegna²  Alain Gelibter²  Enrico Cortesi²  Daniele Marinelli²  Paola Grammatico³  Irene Bottillo³  Giuseppe Giannini⁴  Francesca Belardinilli⁴ 

[1] Cancer Liquid Biopsy Unit, Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy;Department of Radiology, Oncology and Pathology, Sapienza University of Rome, 00161 Rome, Italy;Laboratory of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, 00152 Rome, Italy;Laboratory of Molecular Oncology, Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy;

关键词: KRAS G12C;    liquid biopsy;    clonal evolution;    non-small-cell lung cancer;    circulating tumor DNA;   

DOI  :  10.3390/diagnostics11122196

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown