Molecular Markers of Glioma Initiation and Progression

神经胶质瘤发生和进展的分子标志物

• 批准号: 6756565
• 负责人: ROBERT B. JENKINS
• 金额: $ 199.13万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-14 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6756565
• 关键词: genetic markers; glioma; neoplastic process; neoplastic transformation

DESCRIPTION: (provided by Applicant) Gliomas are a significant cause of morbidity and mortality, and thus have been the focus of frequent basic biologic, basic genetic, and clinical investigations. Numerous genetic and biologic alterations associated with gliomas have been described. However, many of the specific genes involved in gliomas have yet to be identified. A great deal still needs to be learned about the mechanisms by which the known genes are involved in the pathogenesis of gliomas. Furthermore, while much has been learned about the biology and genetics of gliomas, little of this information has been translated into clinical practice. There are still problems with the morphologic classification of gliomas - especially oligodendrogliomas and mixed oligoastrocytomas. It is difficult to predict which patients with anaplastic astrocytomas will suffer early recurrence. And while some gliomas with specific genetic alterations seem to respond to chemotherapy (e.g., Cairncross et al., JNCI 90:1473,1998), these observations need to be confirmed and extended and additional therapeutic genetic targets identified and/or developed. Through four projects and two cores this program, which builds on the past experience of the Glioma Marker Network (GMN) consortium, will study the basic biology of several specific biochemical and genetic alterations associated with gliomas. It will also continue to evaluate the predictive, prognostic, and pathologic relevance of these alterations. Project 1 will study the biologic and clinical relevance of 7q gain in gliomas, with emphasis on the mechanism by which this alteration predicts a poorer prognosis. Project 2 will evaluate the function of mutated and amplified EGFR in gliomas and will test several potential therapeutic approaches targeting these mutant receptors. Project 3 will identify and study the function of the 19q gene associated with gliomas and associated with a prolonged response of some gliomas to chemotherapy. Project 4 will study the biologic and clinical relevance of glycolipid and glycosyltransferase alterations in gliomas. Thus, through these projects, this highly-interactive and experienced program will make significant progress toward understanding the pathogenesis of gliomas, and translating this knowledge into new diagnostic and therapeutic tools.

描述：（申请人提供） 神经胶质瘤是发病率和死亡率的重要原因，因此 频繁的基本生物学，基本遗传和临床的重点 调查。 许多遗传和生物学改变与 胶质瘤已被描述。 但是，许多涉及的特定基因 神经胶质瘤尚未确定。 仍然需要学习很多 关于已知基因参与发病机理的机制 神经胶质瘤。 此外，尽管已经了解了有关生物学和 神经胶质瘤的遗传学，这些信息很少被翻译成 临床实践。 形态学仍然存在问题 神经胶质瘤的分类 - 尤其是少突可瘤和混合 寡聚腹部。 很难预测哪些主体患者 星形胶质细胞瘤将早日复发。 而有些神经瘤与 特定的遗传改变似乎对化学疗法有反应（例如，凯恩克罗斯（Cairncross） 等，JNCI 90：1473，1998），这些观察结果需要确认，并且 确定和/或 发达。 通过四个项目和两个核心，该计划以 神经胶质瘤标记网络（GMN）财团的过去经验将研究 几种特定生化和遗传改变的基本生物学 与神经胶质瘤相关。 它还将继续评估预测性， 这些改变的预后和病理相关性。 项目1将 研究7Q增益在神经胶质瘤中的生物学和临床相关性，重点 关于这种改变预测预后较差的机制。 项目2将评估神经胶质瘤中突变和扩增的EGFR的功能 并将测试针对这些突变体的几种潜在的治疗方法 受体。 项目3将识别和研究19Q基因的功能 与神经胶质瘤相关，并与某些人的长期响应相关 胶质瘤进行化学疗法。 项目4将研究生物学和临床 胶质瘤中糖脂和糖基转移酶改变的相关性。 因此， 通过这些项目，这个高度交互和经验丰富的计划将 在理解神经胶质瘤的发病机理方面取得了重大进展， 并将这些知识转化为新的诊断和治疗工具。