As a proof-of-principle, we used two different CNS-specific TVA-transgenic lines (Nestin-tv-a and GFAP-tv-a) to perform functional characterization of various genetic alterations described in human gliomas: (1) knockout of a panel of TSGs recurrently lost or mutated in GBMs (TP53, CDKN2A and PTEN), (2) genomic rearrangements identified in different subtypes of gliomas (BCAN-NTRK1 and MYB-QKI) and (3) a point mutation (BRAFV600E) present in a variety of pediatric and adult gliomas. The gene discussed is CDKN2A; the disease is central nervous system cancer.