Mus musculus Transcriptome or Gene expression

Glioblastoma(GBM) accounts for up to 50% of brain parenchymal tumors. It is the most malignant type of brain cancer with very poor survival and limited remedies. Cancer subtyping is important for cancer research and therapy. Here, we report a subtyping method for GBM based on genetic alterations. CDKN2A and TP53 are the most frequently mutated genes with mutation rates of 60% and 30% respectively. We found that patients with deletion of CDKN2A possess worse survival than those with mutated TP53. Interestingly, survival of patients with both mutated TP53 and deleted CDKN2A is no worse than for those with only one of these genetic alterations, but similar to those with the TP53 mutation alone. Next, we investigated differences in the gene expression profile between TP53 and CDKN2A samples. Consistent with the survival data, the samples with both TP53 mutation and CDKN2A deletion showed a gene expression profile similar to those samples with only the TP53 mutation. Finally, we found that activation of the RAS pathway via overexpression of H-RASG12V plus Cdkn2a/b silencing can induce GBM, in a similar way to overexpression of H-RASG12V plus TP53 silencing. In conclusion, we show that the genetic alterations of CDKN2A and TP53 may be used to stratify GBM, and we generated animal models of the main subtypes.