Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Cancer Cell. 2011 Mar 8;19(3):305-16. doi: 10.1016/j.ccr.2011.01.039.
Mutations in the PTEN, TP53, and RB1 pathways are obligate events in the pathogenesis of human glioblastomas. We induced various combinations of deletions in these tumor suppressors in astrocytes and neural precursors in mature mice, resulting in astrocytomas ranging from grade III to grade IV (glioblastoma). There was selection for mutation of multiple genes within a pathway, shown by somatic amplifications of genes in the PI3K or Rb pathway in tumors in which Pten or Rb deletion was an initiating event. Despite multiple mutations within PI3K and Rb pathways, elevated Mapk activation was not consistent. Gene expression profiling revealed striking similarities to subclasses of human diffuse astrocytoma. Astrocytomas were found within and outside of proliferative niches in the adult brain.
PTEN、TP53 和 RB1 通路中的突变是人类胶质母细胞瘤发病机制中的必然事件。我们在成熟小鼠的星形胶质细胞和神经前体细胞中诱导这些肿瘤抑制因子的各种缺失组合，导致从 III 级到 IV 级（胶质母细胞瘤）的星形细胞瘤。在一个通路中，多个基因的突变被选择，这是由 Pten 或 Rb 缺失作为起始事件的肿瘤中 PI3K 或 Rb 通路中的基因的体细胞扩增所证明的。尽管在 PI3K 和 Rb 通路中有多个突变，但 Mapk 的激活并不一致。基因表达谱分析显示与人类弥漫性星形细胞瘤的亚类具有惊人的相似性。星形细胞瘤存在于成年大脑的增殖龛内和周围。
