In addition, while human astrocytes engineered with combinations of human TERT and H-Ras expression and inhibition of the TP53 pathway either by SV40 T/t-Ag or by HPV E6 and E7 generate gliomas with high-grade histology5,6, how well these models recapitulate the full spectrum of glioma pathobiology, especially in terms of GBM heterogeneity, has not been well defined. This evidence concerns the gene HRAS and central nervous system cancer.