*Current Utility and Future Applications of ctDNA in Colorectal Cancer DOI: http://dx.doi.org/10.5772/intechopen.82316*

A variety of tumour-specific molecular alterations may be identified by ctDNA including mutations, methylation variants, microsatellite alterations, copy number variations and structural changes [12]. Although the exact mechanisms are yet to be elucidated, ctDNA is thought to be released into the blood stream via biological processes such as apoptosis, necrosis, inefficient phagocytosis and active secretion [13, 14]. CtDNA has a short half-life of up to a few hours and accounts for generally only a small fraction of cfDNA, although concentration can vary widely from <0.01 to 90% [12]. The biological and tumoural determinants underlying ctDNA variations both between and within individuals are incompletely understood, but are likely affected by tumour burden, treatment response, circulatory elements, circadian rhythm, cellular turnover and clearance mechanisms [12, 15]. Somatic variants may also be found in healthy individuals, mostly commonly associated with clonal haematopoiesis [5]. Such variability, coupled with the often-low allele frequency of the molecular aberration of interest, demand sensitive and robust detection methods. As we interpret the results of ctDNA studies and consider their clinical relevance, it is prudent to reflect on these biological variables.
