Genetic alteration and mutation profiling of circulating cell-free tumor DNA (cfDNA) for diagnosis and targeted therapy of gastrointestinal stromal tumors

摘要: Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive type of tumor, different from smooth muscle and neural the gastrointestinal tract. The identification genetic aberrations in proto-oncogenes that drive growth GISTs is critical for improving efficacy cancer therapy by matching targeted drugs to specific mutations. Research into oncogenic mechanisms has found these frequently contain activating gene mutations either platelet-derived factor receptor A (PDGFRA) or tyrosine protein associated with mast cell encoded KIT gene. Mutant subpopulations potential disrupt durable patient responses molecularly GISTs, yet prevalence size remain largely unexplored. Detection harbor low-frequency mutant alleles target through use molecular methods, such polymerase chain reaction (PCR) amplification technology, hampered high abundance wild-type alleles, which limit sensitivity detection minor alleles. This especially true case tumor DNA derived “driver” “drug-resistant” are present circulating cell-free (cfDNA) peripheral blood circulation GIST patients. So-called “liquid biopsy” allows dynamic monitoring patients’ status during treatment using minimally invasive sampling. New methodologies, technology employs xenonucleic acid (XNA) clamping probe block PCR templates, allowed improved both tissue biopsy samples cfDNA. These new methodologies could be widely applied testing therapeutic management GISTs.