New scientific results for targeted therapies for mucosal melanoma

We demonstrated that VS is associated with recurrently amplified regions and identified novel candidate oncogenes (TRPM7, GABPB1 and SPPL2A) for MM. Our results suggest the existence of two molecular subgroups of MM that may benefit from dedicated therapies, such as immune checkpoint inhibitors or targeted therapies, in both human and veterinary medicine. Mucosal melanoma (MM) is a rare and aggressive clinical cancer. Despite recent advances in genetics and treatment, the prognosis of MM remains poor. Canine MM provides a relevant spontaneous and immunocompetent model to decipher the genetic basis and explore treatments for MM. We performed an integrative genomic and transcriptomic analysis of 32 canine MM samples, which identified two molecular subgroups with different microenvironment and structural variant (SV) content. Overexpression of genes related to the microenvironment and T-cell response was associated with tumors with lower SV content, whereas overexpression of pigmentation-related pathways and oncogenes, such as TERT, was associated with high SV load. Using whole genome sequencing, we showed that focal amplifications characterized complex chromosomal rearrangements targeting oncogenes, such as MDM2 or CDK4, and a recurrently amplified region on canine chromosome 30. We also demonstrated that the genes TRPM7, GABPB1, and SPPL2A, located in this CFA30 region, play a role in cell proliferation, and thus can be considered as novel candidate oncogenes for human MM. Our results suggest the existence of two molecular subgroups of MM that could benefit from specific therapies, such as immune checkpoint inhibitors or targeted therapies, in both human and veterinary medicine.

Contact:

• Anaïs Prouteau