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Circulating free tumor DNA and colorectal cancer.

Cancer is characterized by multiple somatic genetic and epigenetic alterations that could be useful as molecular markers for detecting tumor DNA in different bodily fluids. In patients with various diseases as well as in healthy subjects, circulating plasma and serum carry small amounts of non-cell-bound DNA. In this free circulating DNA, tumor-associated molecular alterations can be detected in patients who have cancer. In many instances, the alterations identified are the same as those found in the primary tumor tissue, thereby suggesting tumor origin from a fraction of the circulating free DNA. In fact, various types of DNA alterations described in colorectal cancer have been detected in the circulating free DNA of patients with colorectal cancer. These alterations include KRAS2, APC and TP53 mutations, DNA hypermethylation, microsatellite instability (MSI) and loss of heterozygosity (LOH). Also, advances in polymerase chain reaction (PCR)-based technology now allow the detection and quantification of extremely small amounts of tumor-derived circulating free DNA in colorectal cancer patients. The present report summarizes the literature available so far on the mechanisms of circulating free DNA, and on the studies aimed at assessing the clinical and biological significance of tumor-derived circulating free DNA in colorectal cancer patients. Thus, tumor-derived circulating free DNA could serve as a marker for the diagnosis, prognosis and early detection of recurrence, thereby significantly improving the monitoring of colorectal cancer patients.

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