Serrano C, Vivancos A, López-Pousa A, et al. - Commonly, KIT/PDGFRA oncogenic activation frames gastrointestinal stromal tumor (GIST) initiation and evolution, and in later stages, it is framed by the polyclonal expansion of resistant subpopulations harboring KIT secondary mutations after the onset of imatinib resistance. Researchers investigated if circulating tumor (ct)DNA determination could serve as an informative non-invasive dynamic biomarker in GIST patients. In 37 plasma samples from 18 GIST patients collected prospectively, amplicon-based next-generation sequencing (NGS) was done across 60 clinically relevant genes. A comparison of ctDNA alterations with NGS of matched tumor tissue samples (obtained either simultaneously or at the time of diagnosis) was done and its cross-validation was performed with droplet digital PCR (ddPCR). KIT primary and secondary mutations were identified in metastatic GIST patients via ctDNA evaluation with amplicon-based NGS, especially after imatinib progression. Low ctDNA shedding was observed in GIST, however, ctDNA monitoring, when positive, indicates tumor dynamics.