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 new subtyping method for GBM based on the genetic alterations of CDKN2A and TP53 genes. 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 TP53 mutation. Interestingly, survival of patients with both TP53 mutation and CDKN2A deletion is no worse than for those with only one of these genetic alterations, but similar to those with 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 TP53 mutation alone. Finally, we found that activation of RAS pathway plus Cdkn2a/b silencing can induce GBM, in a similar way to tumor induction by RAS activation plus TP53 silencing. In conclusion, we show that the genetic alterations of CDKN2A and TP53 may be used to stratify GBM, and the new animal models matching this stratification method were generated.

中文翻译：

---

鉴定胶质母细胞瘤亚型和建立相应动物模型的新方法。

胶质母细胞瘤（GBM）占脑实质肿瘤的50％。它是最恶性的脑癌，生存率很低，治疗方法也很有限。癌症亚型对癌症的研究和治疗很重要。在这里，我们报告基于CDKN2A和TP53基因的遗传变异的GBM的一种新的分型方法。CDKN2A和TP53是最常见的突变基因，突变率分别为60％和30％。我们发现，CDKN2A缺失的患者的生存率比TP53突变的患者差。有趣的是，同时具有TP53突变和CDKN2A缺失的患者的存活率并不比仅具有这些遗传变异之一的患者差，但与仅具有TP53突变的患者相似。接下来，我们调查了TP53和CDKN2A样品之间基因表达谱的差异。与存活数据一致，具有TP53突变和CDKN2A缺失的样品显示的基因表达谱与仅具有TP53突变的样品相似。最后，我们发现RAS通路加Cdkn2a / b沉默的激活可以诱导GBM，这与RAS激活加TP53沉默的肿瘤诱导相似。总之，我们表明CDKN2A和TP53的遗传变异可用于对GBM进行分层，并生成了与该分层方法相匹配的新动物模型。