Detection and Diagnostic Utilization of Cellular and Cell-Free Tumor DNA

Because cancer is caused by an accumulation of genetic mutations, mutant DNA released by tumors can be used as a highly specific biomarker for cancer. Although this principle was described decades ago, the advent and falling costs of next-generation sequencing have made the use of tumor DNA as a biomarker increasingly practical. This review surveys the use of cellular and cell-free DNA for the detection of cancer, with a focus on recent technological developments and applications to solid tumors. It covers (a) key principles and technology enabling the highly sensitive detection of tumor DNA; (b) assessment of tumor DNA in plasma, including for genotyping, minimal residual disease detection, and early detection of localized cancer; (c) detection of tumor DNA in body cavity fluids, such as urine or cerebrospinal fluid; and (d) challenges posed to the use of tumor DNA as a biomarker by the phenomenon of benign clonal expansions.