Molecular Markers of Glioma Initiation and Progression

描述：(申请人提供) 胶质瘤是发病率和死亡率的重要原因，因此一直是 常见的基础生物学、基础遗传学和临床的焦点 调查。大量的遗传和生物变化与 胶质瘤已经被描述过了。然而，许多特定的基因参与了 神经胶质瘤尚未被确认。还有很多东西需要学习 关于已知基因参与发病的机制 神经胶质瘤的症状。此外，虽然人们已经学到了很多关于生物学和 神经胶质瘤的遗传学，这些信息中很少被转化为 临床实践。在形态上还是有问题的 胶质瘤的分类--尤其是少突胶质瘤和混合性胶质瘤 少突星形细胞瘤。很难预测哪些间变性患者 星形细胞瘤会出现早期复发。虽然一些胶质瘤有 特定的基因改变似乎对化疗有反应(例如，凯恩克罗斯 等人，JNCI 90：1473,1998)，这些观察结果需要得到证实和 已确定的扩展和附加治疗性基因靶点和/或 发展起来的。通过四个项目和两个核心，该计划建立在 将研究Glioma Marker Network(GMN)联盟过去的经验 几种特殊生化和遗传变化的基础生物学 与神经胶质瘤有关。它还将继续评估可预测的、 这些改变的预后和病理相关性。项目1将 研究胶质瘤中7q增加的生物学和临床相关性，重点是 关于这种改变预测预后更差的机制。 项目2将评估突变和扩增的EGFR在胶质瘤中的功能 并将测试针对这些突变的几种潜在的治疗方法 感受器。项目3将鉴定和研究19q基因的功能。 与胶质瘤有关，并与某些长期反应有关 从胶质瘤到化疗。项目4将研究生物和临床。 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，这个高度互动和经验丰富的项目将 在了解胶质瘤的发病机制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。

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.