MOLECULAR CYTOGENETICS AND RADIATION RESPONSE IN MALIGNANT ASTROCYTOMA

加州大学旧金山分校的恶性星形细胞瘤的治疗是手术后的 辅助放射治疗和化疗。这项提议使用了一种基因 恶性星形细胞瘤的评估和治疗方法。我们的目标是 放射治疗的分析，因为它是最成功的 辅助治疗，因为有三组明确的患者： 那些肿瘤通过放射治疗而进展的患者 他们的肿瘤在放射治疗期间稳定下来，以及他们的肿瘤 尺寸变小。我们假设肿瘤对辐射的敏感性 取决于遗传因素。因此，遗传物质的损失或获得 在任何决定辐射敏感度的位置都应该影响 肿瘤对辐射有反应。因为有许多可能的地点 辐射反应的遗传调控，该提案的第一阶段 包括对原发星形细胞肿瘤和细胞系的几项研究，以 确定星形细胞脑瘤的广泛遗传病理。 对不同级别星形细胞瘤基因改变的认识 肿瘤应该导致了解哪些病变是相关的 与启蒙有关，并与进步有关。在第二个 阶段，我们将询问这些病变中是否有任何有助于临床 患者对辐射的反应。 具体目标是：1)识别和绘制在以下方面的损失或收益区域 来自胶质瘤细胞系、原发人脑胶质瘤以及原发和 复发性恶性胶质瘤对；2)比较放射敏感性和 抗辐射肿瘤遗传物质的损失和获得 目标1中定义的基因座；以及，3)将在 使用CORE进行临床和实验室观察的目标1和2 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.