Mutational Signatures in Cancer Laboratory Considerations and Emerging Applications

Patterns of somatic mutations have emerged from the broad sequencing of human cancer genomes. These mutational signatures reflect mechanisms of mutagenesis and DNA repair defects and represent an emerging class of cancer biomarkers. The appropriate interpretation of mutational signatures from sequencing assays holds implications in the reporting of molecular diagnostic results for patients with cancer. This brief review describes the scientific principles, laboratory considerations, and emerging clinical applications of mutational signature analysis from clinical cancer genomes. (J Mol Diagn 2023, 25: 790-795; https://doi.org/10.1016/j.jmoldx.2023.08.002)

Automated summary

Patterns of somatic mutations, known as mutational signatures, have been identified through the sequencing of human cancer genomes. These signatures provide insights into the mechanisms and DNA repair defects underlying mutagenesis, and hold promise as emerging cancer biomarkers. Accurate interpretation of mutational signatures in sequencing assays is crucial for reporting molecular diagnostic results for cancer patients. This brief review presents the scientific principles, laboratory considerations, and emerging clinical applications of mutational signature analysis from clinical cancer genomes.