Mercoledì del PRIN n.9: Marianna Flora Tomasello/Noemi Anna Pesce

Mutational map of extracellular and vescicular DNA and effects on horizontal gene transfer in Uveal Melanoma

Dr. Marianna Flora Tomasello and Dr. Noemi Anna Pesce

Uveal Melanoma (UM) is a rare form of melanoma but the most frequent and aggressive primary ocular tumor in adults with about50% of patients developing metastasis with fatal outcome notwithstanding medical treatment. UM shows a low mutational burden and just few mutually exclusive driver mutations with relevant diagnostic/prognostic significance occurring in patients.Unfortunately, UM biopsy is scarcely practicable as the tissue should be extracted from the eye after its enucleation, making amutational screening for diagnosis unfeasible. Recently, the idea that cancer cells are able to release DNA in extracellularenvironment has been partially explored. The sequencing of extracellular DNA (exDNA) from biological fluids of patients can be exploited to identify mutations originating from tumor cells and, accordingly, carry out non-invasive mutational screening for diagnostics and prognostics. Furthermore, tumoral exDNA could be internalized by other cells thus contributing to the molding of the tumor microenvironment. Based on these premises, we propose a project with twofold aim. 1) To detect UM driver mutations in 3 different biological fluids from UM patients (ie, serum, humor vitreous, humor aqueous) and their corresponding extracellular vesicle fractions 2) To investigate whether and how UM cells can transfer their exDNA to cells belonging to tumor microenvironment and detect the functional effects. The expected results of the project will lay the foundations for the development of pre-designed panels for UM driver mutations to be tested on exDNA from patients, enabling non-invasive diagnostic and prognostic approaches.

Keywords

1. Uveal Melanoma driver mutations (mutazioni driver del melanoma uveale)
2. Extracellular Vesicles (vescicole extracellulari)
3. horizontal gene transfer (trasferimento genico orizzonatle)