Since cancer-associated mutations in liquid biopsies compromise the specificity of DNA sequencing tests for cancer detection and minimal residual disease tracking, this article highlights approaches to address this issue.
Sequencing of normal tissues has revealed abundant mutations in cancer-associated genes, which increase with age across different tissues. Thus, mutations in certain cancer genes are not specific to cancer, but a normal phenotype of aging. These findings reveal somatic evolution and are consistent with cancer as a multistep process. Precancerous cells likely exist along a genetic continuum and only rarely culminate in clinically defined cancer. Tumor suppressor mechanisms are critical to stop the progression of mutated clones. The weakening of these mechanisms at late age and/or the bypass by additional mutations renders pre-existing clones susceptible to malignant transformation. (publisher abstract modified)