Fig. 2

Mutational signature analysis as a tool in cancer diagnostics. A patient who is diagnosed with cancer will undergo biopsy of both the tumor tissue and a healthy tissue sample (e.g. blood). The entire DNA of both specimens will then be read using whole-genome sequencing (WGS), which allows the characterization of somatic mutations in the form of base substitutions, indels, rearrangements, copy-number variations (CNVs) and variations thereof. The healthy sample can be used to characterize predisposition variants, and somatic events can identify potentially actionable somatic tumor driver variants. Mutational signature analysis can provide additional evidence to support the interpretation of these measurements, such as for the interpretation of Variants of Unknown Significance (horizontal arrows), but can also provide direct support for the cancer diagnosis. The result of this workflow will influence clinical interventions such as treatment decisions and family counseling if a predisposition variant has been identified, and allows for stratification of patients towards effective anti-cancer drugs (precision medicine) to improve the patient’s outcome (prognosis)