<scp>UV</scp> Signature Mutations

<jats:title>Abstract</jats:title><jats:p>Sequencing complete tumor genomes and exomes has sparked the cancer field's interest in mutation signatures for identifying the tumor's carcinogen. This review and meta‐analysis discusses signatures and their proper use. We first distinguish between a mutagen's <jats:italic>canonical mutations</jats:italic>—deviations from a random distribution of base changes to create a pattern typical of that mutagen—and the subset of <jats:italic>signature mutations</jats:italic>, which are unique to that mutagen and permit inference backward from mutations to mutagen. To verify <jats:styled-content style="fixed-case">UV</jats:styled-content> signature mutations, we assembled literature datasets on cells exposed to <jats:styled-content style="fixed-case">UVC</jats:styled-content>,<jats:styled-content style="fixed-case"> UVB</jats:styled-content>,<jats:styled-content style="fixed-case"> UVA</jats:styled-content>, or solar simulator light (<jats:styled-content style="fixed-case">SSL</jats:styled-content>) and tested canonical <jats:styled-content style="fixed-case">UV</jats:styled-content> mutation features as criteria for clustering datasets. A confirmed <jats:styled-content style="fixed-case">UV</jats:styled-content> signature was: ≥60% of mutations are C→T at a dipyrimidine site, with ≥5% <jats:styled-content style="fixed-case">CC</jats:styled-content>→<jats:styled-content style="fixed-case">TT</jats:styled-content>. Other canonical features such as a bias for mutations on the nontranscribed strand or at the 3′ pyrimidine had limited application. The most robust classifier combined these features with criteria for the rarity of non‐<jats:styled-content style="fixed-case">UV</jats:styled-content> canonical mutations. In addition, several signatures proposed for specific <jats:styled-content style="fixed-case">UV</jats:styled-content> wavelengths were limited to specific genes or species; UV's nonsignature mutations may cause melanoma <jats:italic><jats:styled-content style="fixed-case">BRAF</jats:styled-content></jats:italic> mutations; and the mutagen for sunlight‐related skin neoplasms may vary between continents.</jats:p>