A study conducted by scientists at the Institute of Oncology Research (IOR, affiliated with USI and a member of Bios+) in collaboration with researchers specialized in veterinary oncology at the Universities of Turin and Bologna, identified the most frequent mutations in diffuse large B-cell lymphoma (DLBCL), one of the most frequent tumors in both humans and dogs, opening new therapeutic opportunities. The study is published in Lab Animal, a monthly international scientific journal of Nature portfolio.
Diffuse large B-cell lymphoma (DLBCL) is one of the most common cancers in both humans and dogs. However, despite improvements in outcome, the clinical response to the treatment remains often unpredictable, especially in dogs where death related to lymphoma is very frequent and the survival time is very low (approximately one year).
Within this context human and canine DLBCL are very similar, indeed several molecules to treat human lymphomas, now approved by American and European regulatory agencies, have been tested in several canine clinical trials with positive results. However, it is fundamental to study the DLBCL pathogenesis in dogs to identify homologies and differences with the human counterpart.
In the paper recently published in Lab Animal journal, where a collaboration between scientists at the Institute of Oncology Research (IOR, affiliated with USI and a member of Bios+) and researchers with expertise in veterinary comparative oncology at the Universities of Turin and Bologna was established, the most frequent mutations in canine DLBCL were identified, some of them had also a prognostic and potentially therapeutic significance.
The two corresponding authors, Prof. Francesco Bertoni, Group Leader at IOR and Prof. Luca Aresu, Group Leader of the Canine Comparative Oncology Lab at the University of Turin, in collaboration with Prof. Laura Marconato of the University of Bologna identified the most frequent mutations affecting the proteins-coding genes of the whole genome that are involved in transcription regulation (that is, the transfer of genetic information from DNA to RNA). Most of the genetic lesions were similar to the recurrent lesions identified in human DLBCL, revealing the potential of a particular class of drugs, such as epigenetic molecules, that the IOR group has been developing in the recent years. The study also makes light it in defining other potential targets to test in dogs with DLBCL before translating to humans, but also offering new opportunities to dogs with lymphoma as well.
Lastly, the research also demonstrated the role of TP53 gene mutations in predicting response to therapy in canine DLBCL and guiding the decision-treatment strategy by the owner, which is now possible through a predictive model available on an online platform (https://compbiomed.hpc4ai.unito.it/canine-dlbcl/). The role of TP53 mutations was already demonstrated in several human lymphomas but not yet in the canine species