Characterization of GEFT AS a Novel Glioblastoma Oncogene

胶质母细胞瘤（GBM）是最常见和致命的原发性中枢神经系统肿瘤。最 积极治疗，中位生存期为14.6个月。到目前为止，还没有一个系统的方法， 验证体细胞扩增的候选基因在胶质瘤发病机制中的作用。 这些基因可能在驱动肿瘤发生中发挥直接作用，或者肿瘤细胞可能依赖于它们来产生肿瘤。 存活和增殖，这一过程被称为“癌基因成瘾”。“因此，这些途径具有吸引力， 治疗的目标我进行了一个RNA干扰筛选，目标是在基因组中通常扩增的区域上的基因。 GBM和鉴定GEFT，鸟嘌呤核苷酸交换因子（GEF），作为GBM细胞增殖所必需的 和/或生存能力。使用遗传和生物化学方法，我建议表征GEFT及其蛋白质- 蛋白质相互作用我将测试GEFT的抑制如何调节细胞生长和/或存活，并测试是否过度- 表达足以将遗传上明确定义的永生化星形胶质细胞转化为恶性胶质瘤 状态此外，我将确定GEFT对细胞增殖和/或存活的效应物。 相关性（参见说明）： 胶质母细胞瘤（GBM）是最常见和致命的原发性脑肿瘤。最具侵略性的 中位生存期为14.6个月。我建议描述一个基因，GEFT，这可能会发挥作用， 这些肿瘤的形成和维持。

Glioblastomas (GBM) are the most common and lethal primary central nervous system tumors. With the most aggressive therapy, median survival is 14.6 months. To date, there has not been a systematic approach to validate the function of candidate genes that are somatically amplified, for their role in glioma pathogenesis. These genes might play direct roles driving tumorigenesis, or tumor cells might depend on them for their survival and proliferation, a process known as "oncogene addiction." Therefore, these pathways are attractive targets for therapy. I performed an RNA interference screen targeting genes on regions commonly amplified in GBM and identified GEFT, a guanine nucleotide exchange factor (GEF), as essential for GBM cell proliferation and/or viability. Using genetic and biochemical approaches, I propose to characterize GEFT and its protein- protein interactions. I will test how suppression of GEFT regulates cell growrth and/or survival, and test if over- expression is sufficient to transform genetically well defined, immortalized astrocytes into a malignant glioma state. Additionally, I will determine the effector(s) of GEFT for cell proliferation and/or survival. RELEVANCE (See instructions): Glioblastomas (GBM) are the most common and lethal primary brain tumors. With the most aggressive therapy, median survival is 14.6 months. I propose to characterize a gene, GEFT, that might play a role in formation and maintenance of these tumors.