Cancer mutation signatures, DNA damage mechanisms, and potential clinical implications

Abstract

Knowledge of cancer genomic DNA sequences has created unprecedented opportunities for mutation studies. Computational analyses have begun to decipher mutational signatures that identify underlying causes. A recent analysis encompassing 30 cancer types reported 20 distinct mutation signatures, resulting from ultraviolet light, deficiencies in DNA replication and repair, and unexpectedly large contributions from both spontaneous and APOBEC-catalyzed DNA cytosine deamination. Mutational signatures have the potential to become diagnostic, prognostic, and therapeutic biomarkers as well as factors in therapy development.

Figure 1

External and internal sources of mutation in cancer. A schematic depiction of major external and internal sources of DNA damage, a variety of DNA repair mechanisms that serve to counteract damage, and mutation as an outcome of unrepaired DNA damage.