That the combined loss of p16INK4A and p18INK4C function confers enhanced malignant potential over that associated with p16INK4A loss alone in human GBM cells was further substantiated by demonstration that tumor-associated p18INK4C variants occurring at highly conserved residues (p.F37I in GB-1 and p.A61D in KNS-60; Figure S3) were loss-of-function mutants. Here, GABBR1 is linked to neoplasm.