Global InformationCirculating tumor DNA information
Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA in the bloodstream that is not associated with cells. ctDNA should not be confused with cell-free DNA (cfDNA), a broader term which describes DNA that is freely circulating in the bloodstream, but is not necessarily of tumor origin. Because ctDNA may reflect the entire tumor genome, it has gained traction for its potential clinical utility; "liquid biopsies" in the form of blood draws may be taken at various time points to monitor tumor progression throughout the treatment regimen.[1][2]
Recent studies have laid the foundation for inferring gene expression from cfDNA (and ctDNA), with EPIC-seq emerging as a notable advancement.[3] This method has substantially raised the bar for the noninvasive inference of expression levels of individual genes, thereby augmenting the assay's applicability in disease characterization, histological classification, and monitoring treatment efficacy.[3][4][5]
ctDNA originates directly from the tumor or from circulating tumor cells (CTCs),[6] which describes viable, intact tumor cells that shed from primary tumors and enter the bloodstream or lymphatic system. The precise mechanism of ctDNA release is unclear. The biological processes postulated to be involved in ctDNA release include apoptosis and necrosis from dying cells, or active release from viable tumor cells.[7][8][9][10][11] Studies in both human (healthy and cancer patients)[12] and xenografted mice[13] show that the size of fragmented cfDNA is predominantly 166bp long, which corresponds to the length of DNA wrapped around a nucleosome plus a linker. Fragmentation of this length might be indicative of apoptotic DNA fragmentation, suggesting that apoptosis may be the primary method of ctDNA release. The fragmentation of cfDNA is altered in the plasma of cancer patients.[14][15] In healthy tissue, infiltrating phagocytes are responsible for clearance of apoptotic or necrotic cellular debris, which includes cfDNA.[16] ctDNA in healthy patients is only present at low levels but higher levels of ctDNA in cancer patients can be detected with increasing tumor sizes.[17] This possibly occurs due to inefficient immune cell infiltration to tumor sites, which reduces effective clearance of ctDNA from the bloodstream.[16] Comparison of mutations in ctDNA and DNA extracted from primary tumors of the same patients revealed the presence of identical cancer-relevant genetic changes.[18][19] This led to the possibility of using ctDNA for earlier cancer detection and treatment follow up.[20]
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- ^ Mutter, Jurik A; Shahrokh Esfahani, Mohammad; Schroers-Martin, Joseph; et al. (28 November 2023). "Inferred Gene Expression By Cell-Free DNA Profiling Allows Noninvasive Lymphoma Classification". Blood. 142 (Supplement 1): 245–245. doi:10.1182/blood-2023-186853.
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