MOLECULAR BIOMARKERS IN THE CLASSIFICATION OF GLIMOAS

GLIMOAS 分类中的分子生物标志物

• 批准号: 2008599
• 负责人: PETER C BURGER
• 金额: $ 23.86万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-19 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2008599
• 关键词: astrocytoma; biomarker; biopsy; cancer risk; complementary DNA; gel electrophoresis; gene mutation; genetic markers; glioma; human subject; messenger RNA; molecular oncology; neoplasm /cancer classification /staging; neoplasm /cancer diagnosis; neoplasm /cancer invasiveness; oligodendroglia; polymerase chain reaction; prognosis; restriction fragment length polymorphism

The goals of this study are to identify and evaluate molecular markers useful in the classification and grading of gliomas. The intended projects, as listed in the Specific Aims, were selected so as to address problems in tumor classification whose resolution, we believe, will significantly improve the diagnosis, and therefore treatment, of patients with brain tumors. These issues include: (1) the details and diagnostic specificity of molecular changes in spectrum of pilocystic astrocytomas arising in both patients with neurofibromatosis 1 and in the general population without a recognized genetic predisposition to this common pediatric neoplasm, (2) the presence or absence of similar molecular changes in sporadic non-pilocystic tumors (high grade fibrillary astrocytic tumors and oligodendrogliomas) and how these might be related to tumor classification, (3) the prognostic utility in higher grade astrocytic neoplasms of the cycling cell marker Ki-67 and amplification of the epidermal growth factor receptor gene, (4) the genomic abnormalities associated with tumor progression in fibrillary astrocytic and oligodendroglial neoplasms, and how these changes can be used in tumor grading and prognosis, and (5) the determination of tumor extent (staging) of the untreated glioblastoma by unambiguous molecular methods. The proposed research benefits from strong interactions with the multicenter CNS Consortium New Approaches to Brain Tumor Therapy (NABTT). NABTT will provide ready access to rare tissue resources and the extensive clinical and scientific data from a large collection of patients diagnosed with primary gliomas required for our analyses. Our molecular findings derived from PCR-based highly efficient methods will be correlated with clinical parameters including the response to specific NABTT initiated treatments. Close interactions between our Cooperative Glioma Network multidisciplinary research team and the NABTT will significantly extend the resources of both studies. These studies will improve our knowledge of the molecular alterations of these tumors and provide diagnostic markers that can be correlated with outcome. Moreover, these data will provide the basis for future studies on the pathophysiologic mechanisms of gliomas and lead to new approaches to treatment.

本研究的目的是鉴定和评价分子标记 可用于神经胶质瘤的分类和分级。预期 选择具体目标中所列的项目是为了解决 我们相信，这些问题的解决将 显著改善患者的诊断和治疗 患上了脑瘤这些问题包括：（1）细节和诊断 毛囊性星形细胞瘤分子谱改变的特异性 出现在神经纤维瘤病1型患者和一般患者中 没有公认的遗传易感性的人群，这种常见的 小儿肿瘤，（2）是否存在类似的分子 散发性非毛囊性肿瘤（高级别囊性肿瘤）的变化 星形细胞肿瘤和少突胶质细胞瘤）以及这些肿瘤之间的关系 （3）在高级别肿瘤中的预后价值 星形细胞肿瘤的细胞周期标志物Ki-67及扩增 表皮生长因子受体基因，（4）基因组 星形胶质细胞瘤进展相关异常 和少突胶质细胞肿瘤，以及如何利用这些变化， 肿瘤分级和预后;（5）肿瘤范围的确定 通过明确的分子方法对未经治疗的胶质母细胞瘤进行（分期）。 拟议的研究受益于与 多中心CNS联盟脑肿瘤治疗新方法（NABTT）。 NABTT将提供现成的稀有组织资源， 大量的临床和科学数据， 我们的分析需要诊断为原发性胶质瘤的患者。我们 基于PCR的高效方法的分子发现将 与临床参数相关，包括对特定 NABTT开始治疗。 我们合作社之间的密切互动 神经胶质瘤网络多学科研究小组和NABTT将 大大增加了两项研究的资源。 这些研究将 提高我们对这些肿瘤分子改变的认识， 提供与结果相关的诊断标志物。 此外，这些数据将为未来的研究提供基础。 神经胶质瘤的病理生理机制，并导致新的方法， 治疗