Glioblastoma (GBM) accounts for up to 50% of brain parenchymal tumors. It is the most malignant type of brain cancer withvery poor survival and limited remedies. Cancer subtyping is important for cancer research and therapy. Here, we report anew subtyping method for GBM based on the genetic alterations of CDKN2A and TP53 genes. CDKN2A and TP53 are themost frequently mutated genes with mutation rates of 60 and 30%, respectively. We found that patients with deletion ofCDKN2A possess worse survival than those with TP53 mutation. Interestingly, survival of patients with both TP53 mutationand CDKN2A deletion is no worse than for those with only one of these genetic alterations, but similar to those with TP53mutation 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 expressionprofile similar to those samples with TP53 mutation alone. Finally, we found that activation of RAS pathway plus Cdkn2a/bsilencing can induce GBM, in a similar way to tumor induction by RAS activation plus TP53 silencing. In conclusion, weshow that the genetic alterations of CDKN2A and TP53 may be used to stratify GBM, and the new animal models matchingthis stratification method were generated.

N3, the second most commonly deregulated gene identified in thepresent study, is known to carry a mutation in AD patients. According to functional network analysis, NRXN3 plays a critical role insynaptic functions involved in the cognitive decline associated with normal aging and AD.

Conclusion: Our results indicate that the low expression of aging-related NRXN3 may increase AD risk, though the potentialmechanism requires further clarification.Abbreviations: Ab = amyloid beta, AD = Alzheimer disease, DEGs = differentially expressed genes, FDR = false discovery rate,GEO = Gene Expression Omnibus, JEPETTO = Java Enrichment of Pathways Extended to Topology, KEGG = Kyoto Encyclopediaof Genes and Genomes, MCODE = molecular complex detection, NCBI = National Center for Biotechnology Information, NLGN =neuroligin, NRXN = neurexin, PTPRT = receptor-type tyrosine-protein phosphatase T, RMA = robust multichip average, SAM =significance analysis of microarrays, SNPs = single nucleotide polymorphisms.