Patient-specific somatic mutations in circulating tumor DNA (ctDNA)

Patient-specific somatic mutations in circulating tumor DNA (ctDNA) refer to the genetic alterations identified in cell-free DNA fragments shed by tumor cells into the systemic circulation [1]. These mutations function as a liquid biopsy, providing a non-invasive means to profile the genomic landscape of a patient's malignancy and monitor its evolution over time [2]. While ctDNA itself is not a therapeutic target—as drugs do not interact with these circulating DNA fragments to treat disease—it is a vital diagnostic tool for identifying actionable mutations in proteins like EGFR, KRAS, or BRAF [3]. Clinically, the detection of these mutations is used for early cancer detection, monitoring treatment response, and identifying minimal residual disease (MRD) after surgical intervention [4]. The use of ctDNA allows clinicians to track the emergence of resistance mutations, such as the EGFR T790M mutation, often before they are detectable via traditional imaging [5]. However, challenges remain, including the low concentration of ctDNA in early-stage disease and the potential for false positives arising from clonal hematopoiesis of indeterminate potential (CHIP) [6]. Sources: [1] NCI Dictionary of Cancer Terms; [2] Heitzer et al., Nature Reviews Genetics (2019); [3] Corcoran and Chabner, NEJM (2018); [4] Abbosh et al., Nature (2017); [5] Diehl et al., Nature Medicine (2008); [6] Razavi et al., Nature Medicine (2019).

Other names

Circulating tumor DNALiquid biopsyCell-free tumor DNATumor-derived cell-free DNAPlasma somatic mutations

Not applicable. Patient-specific somatic mutations in ctDNA serve as diagnostic and prognostic biomarkers rather than therapeutic targets for drug binding.