MOLECULAR CYTOGENETICS AND RADIATION RESPONSE IN MALIGNANT ASTROCYTOMA

在加州大学旧金山分校恶性星形细胞瘤的治疗一直是手术， 辅助放疗和化疗。 这项提案使用了一种基因 恶性星形细胞瘤的评估和治疗方法。 我们针对 放射治疗的分析，因为它是最成功的 辅助治疗，因为有三个明确的患者组： 那些肿瘤在放射治疗中进展的病人， 他们的肿瘤在放射治疗期间稳定下来， 尺寸减小。 我们假设肿瘤的辐射敏感性 取决于遗传因素。 因此，遗传物质的损失或获得 在决定辐射敏感性的任何地点， 肿瘤对辐射有反应。 因为有很多可能的地点 辐射反应的遗传调节，第一阶段的建议 包括几项原发性星形细胞肿瘤和细胞系的研究， 确定星形细胞脑肿瘤的广泛遗传病理学。 这种对不同级别星形胶质细胞遗传改变的了解， 肿瘤应导致了解哪些病变是相关的 与起始和进展相关。 在第二 阶段，我们将询问这些病变是否有助于临床 患者的辐射反应。 具体目标是：1）确定和绘制损失或收益区域， 来自神经胶质瘤细胞系、原发性人神经胶质瘤以及原发性和 复发性恶性胶质瘤对; 2）比较放射敏感性和 抗辐射肿瘤的遗传物质的损失和收益. 目标1中定义的基因座;以及，3）将在目标1中获得的该遗传数据与目标2中定义的基因座进行关联。 目的1和2以及使用核心的临床和实验室观察结果 数据库

Therapy for malignant astrocytomas at UCSF has been surgery followed by adjuvant radiation therapy and chemotherapy. This proposal uses a genetic approach for malignant astrocytoma evaluation and treatment. We target radiation therapy for analysis because it is the most successful of the adjuvant therapies, and because there are three clear groups of patients: those whose tumors progress through their radiation therapy, patients whose tumors stabilize during radiation therapy, and those whose tumors decrease in size. We hypothesize that a tumor's radiation sensitivity depends upon genetic factors. Thus, the loss or gain of genetic material at any locus that determines radiation sensitivity should influence how a tumor responds to radiation. Because there are many possible sites for genetic regulation of radiation response, the first stage of the proposal encompasses several studies of primary astrocytic tumors and cell lines to determine a broad range of genetic pathology in astrocytic brain tumors. This knowledge of genetic alterations in different grades of astrocytic neoplasms should lead to an understanding of which lesions are associated with initiation and which are associated with progression. In the second stage, we will ask whether any of these lesions contribute to clinical radiation response in patients. The specific aims are: 1) to identify and map regions of loss or gain in DNA from glioma cell lines, primary human gliomas, and primary and recurrent malignant glioma pairs; 2) to compare radiation- sensitive and radiation-resistant tumors for losses and gains of genetic material at loci defined in Aim 1; and, 3) to correlate this genetic data obtained in Aims 1 and 2 with clinical and laboratory observations using the Core database.