Detection of Circulating Tumor DNA in Solid Tumors

Abstract

Cancer is characterized by sequential and progressive genetic and epigenetic alterations in key proto-oncogenes and tumor suppressor genes, which ultimately lead to tumor development. Advances in the technology of analysis of molecular mechanisms have increased the efficiency of clinical management of cancer patients. Recent years have witnessed a progressive development in technologies that enable the detection of specific molecular abnormalities associated with various types of solid tumors in body fluids, a process that is globally known as "liquid biopsy". Liquid biopsy is largely based on the circulating free DNA (cfDNA) present in the plasma of healthy individuals and derived either from cell apoptosis or from the active secretion of microvesicles mediated by white blood cells (WBCs). The plasma of cancer patients contains DNA, which is referred to as circulating tumor DNA (ctDNA) and is released by the tumor cells in the form of DNA fragments of various sizes bearing the various types of genetic abnormalities specific to the tumors from which were derived. Sequencing studies conducted with several thousands of cancer patients have revealed that ctDNA accounts for only a fraction of the total DNA, and the size of this fraction varies in relation to tumor burden, tumor site, tumor subtypes, and several other biological properties of the tumor cells. Therefore, the levels of ctDNA are extremely low in several earlystage tumors, requiring highly sensitive methods for the detection of genetic alterations