Modrek Aram S, Bayin N Sumru, Placantonakis Dimitris G
Aram S Modrek, Medical Scientist Training Program, New York University School of Medicine, New York, NY 10016, United States.
World J Stem Cells. 2014 Jan 26;6(1):43-52. doi: 10.4252/wjsc.v6.i1.43.
Glioma incidence rates in the United States are near 20000 new cases per year, with a median survival time of 14.6 mo for high-grade gliomas due to limited therapeutic options. The origins of these tumors and their many subtypes remain a matter of investigation. Evidence from mouse models of glioma and human clinical data have provided clues about the cell types and initiating oncogenic mutations that drive gliomagenesis, a topic we review here. There has been mixed evidence as to whether or not the cells of origin are neural stem cells, progenitor cells or differentiated progeny. Many of the existing murine models target cell populations defined by lineage-specific promoters or employ lineage-tracing methods to track the potential cells of origin. Our ability to target specific cell populations will likely increase concurrently with the knowledge gleaned from an understanding of neurogenesis in the adult brain. The cell of origin is one variable in tumorigenesis, as oncogenes or tumor suppressor genes may differentially transform the neuroglial cell types. Knowledge of key driver mutations and susceptible cell types will allow us to understand cancer biology from a developmental standpoint and enable early interventional strategies and biomarker discovery.
美国每年的胶质瘤发病率接近20000例新发病例，由于治疗选择有限，高级别胶质瘤的中位生存时间为14.6个月。这些肿瘤及其众多亚型的起源仍是一个研究课题。来自胶质瘤小鼠模型和人类临床数据的证据提供了有关驱动胶质瘤发生的细胞类型和起始致癌突变的线索，我们在此对这一主题进行综述。关于起源细胞是神经干细胞、祖细胞还是分化后代，证据不一。许多现有的小鼠模型针对由谱系特异性启动子定义的细胞群体，或采用谱系追踪方法来追踪潜在的起源细胞。我们靶向特定细胞群体的能力可能会随着从对成人大脑神经发生的理解中获得的知识而同步提高。起源细胞是肿瘤发生中的一个变量，因为癌基因或肿瘤抑制基因可能会以不同方式转化神经胶质细胞类型。了解关键驱动突变和易感细胞类型将使我们能够从发育角度理解癌症生物学，并实现早期干预策略和生物标志物发现。
