Dipartimento di Ingegneria informatica, automatica e gestionale

Genetic instability is one of the hallmarks of cancer, however mutations can occur for different causes and induce different effects. Mutational signatures are characteristic patterns of somatic mutations in cancer genomes, reflecting the underlying mutational processes. A mutational signature can be determined by studying the kind of mutations a patient has acquired during their life: patient stratification based on mutational signatures has become more and more useful in genomic studies, given its possible clinical implications. In this work we focused on Single Base Substitution (SBS) signatures to study a cohort of 115 metastatic melanoma patients. We inferred and identified two mutational signatures characterizing the patients. Based on these signatures we divided patients into two group: the bigger group was characterized by a signature associated with exposure to ultraviolet light, while the smaller group resulted to be mostly composed of patients which did not respond to immunotherapy (anti-PD1) and that presented a low mutational count. More importantly this second group showed a significantly worse survival outcome. The use of mutational signatures is clearly a powerful tool to identify disease sub-types that have a clinical relevance, however we believe that this topic needs further investigation focused on the characterization of patient subtypes with a multi-omics based approach.