Refining our understanding of the evolutionary mechanisms behind different types of cancer is key to achieving increasingly targeted diagnoses and treatments. A significant step forward comes from the new RESOLVE method, based on the analysis of “mutational signatures” – recurring patterns of DNA mutations that reveal the history of damage experienced by tumour cells and help identify their origin and mechanisms of development.
The analysis of mutational signatures is a well-established practice in cancer genomics, but it presents several challenges. Compared to existing methods, RESOLVE (Robust EStimation Of mutationaL signatures Via rEgularization) offers: more accurate detection of mutational signatures; more reliable estimation of their relevance in individual patients; and the ability to distinguish tumours into molecular subtypes – with promising implications for personalised medicine.
This innovative method, detailed in the article “Comprehensive analysis of mutational processes across 20,000 adult and paediatric tumours” published in Nucleic Acids Research, was developed by a multidisciplinary team at the University of Milano-Bicocca, coordinated by Daniele Ramazzotti (Department of Medicine and Surgery and IRCCS San Gerardo dei Tintori Foundation). The project also involved researchers from the Department of Informatics, Marco Antoniotti and Alex Graudenzi; from the Department of Medicine, Rocco Piazza and Luca Mologni; and Giulio Caravagna from the University of Trieste. The team also includes Matteo Villa, Federica Malighetti, Luca De Sano, Alberto Maria Villa, Nicoletta Cordani, and Andrea Aroldi.
The study presents a new computational tool for analysing the mutational mechanisms underlying cancer. By applying this method to around 20,000 adult and paediatric tumour genomes, the researchers were able to accurately identify a limited number of dominant mutational signatures, associated both with known biological mechanisms (such as ageing, tobacco exposure, or DNA repair deficiencies) and with different clinical prognoses.
“Our study shows that, despite the high heterogeneity of cancer, a relatively small number of mutational processes are responsible for the majority of observed mutations,” says Daniele Ramazzotti, lead author of the study. “This discovery opens new avenues for diagnosis, prognosis, and the development of increasingly targeted therapies in oncology.”