GENETIC AND BIOLOGIC STUDIES OF 1P AND 19Q IN GLIOMAS

胶质瘤中 1P 和 19Q 的遗传学和生物学研究

• 批准号: 6089845
• 负责人: ROBERT B. JENKINS
• 金额: $ 29.24万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-03 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6089845
• 关键词: athymic mouse; chromosome deletion; clinical research; complementary DNA; family genetics; genetic mapping; genetic markers; genomic imprinting; glioma; human subject; loss of heterozygosity; male; neoplasm /cancer classification /staging; neoplasm /cancer genetics; nucleic acid sequence; p53 gene /protein; prostate neoplasms

Alterations of chromosomes 1 and 19 are frequent events in human gliomas and have recently been suggested to be associated with chemotherapeutic response and prolonged survival in anaplastic oligodendrogliomas. However, the genes on these chromosome arms that are altered in gliomas and potentially associated with chemotherapeutic response and survival have not been identified. Furthermore, the exciting response and survival data have not been confirmed in an appropriately-treated, prospectively-collected cohort of patients nor have these clinical correlations been translated to lower grade oligodendrogliomas or other glial tumors. We have made considerable progress in mapping the genomic location of the 19q gene and have identified several genes in this region. In addition, we have assembled several prospectively-collected cohorts of patients to confirm and extend the clinical observations of Caimcross et al. In this application, we propose to 1) Complete the identification of the 19q gene (or genes) involved in the development of gliomas, 2) Begin an evaluation of the function of the 19q gene (or genes), 3) Finely map the minimal 1p deletion region in gliomas, to begin to identify the gene (or genes) on 1p involved in the development of gliomas, and 4) To perform clinical-translational studies designed to validate the postulated predictive value of 1p/19q alterations, to determine if alterations of the specific genes involved have similar associations, and to extend the associations to lower grade tumors and to tumors of different glial lineage. Thus, this project will identify and begin to study the function of the 19q gene, map the 1p deletion region, and further define the clinical significance of the 1p and 19q alterations. The overall result of this project will be an initial understanding of the genetics and biology of the 19q and 1p genes as well as the development of a combined histologic and genotypic assessment of gliomas that could potentially be used to stratify patients for therapy.

1号和19号染色体的改变是人类胶质瘤的常见事件，最近被认为与间变性少突胶质细胞瘤的化疗反应和生存期延长有关。 然而，这些染色体臂上的基因在胶质瘤中发生改变，并可能与化疗反应和生存有关，尚未确定。此外，令人兴奋的反应和生存数据尚未在适当治疗的前瞻性收集的患者队列中得到证实，这些临床相关性也未转化为低级别少突胶质细胞瘤或其他神经胶质肿瘤。 我们已经取得了相当大的进展，在19 q基因的基因组定位，并已确定在该地区的几个基因。 此外，我们还收集了几个前瞻性收集的患者队列，以确认和扩展Caimcross等人的临床观察结果。在本申请中，我们建议1）完成19 q基因的鉴定2）开始评估19 q基因的功能3）精细定位胶质瘤中最小1 p缺失区，开始鉴定基因（或基因）参与神经胶质瘤的发展，和4）进行临床翻译研究，旨在验证1 p/19 q改变的假设预测价值，以确定所涉及的特定基因的改变是否具有类似的关联，并将关联扩展到较低级别的肿瘤和不同神经胶质谱系的肿瘤。 因此，本项目将确定并开始研究19 q基因的功能，绘制1 p缺失区域，并进一步确定1 p和19 q改变的临床意义。 该项目的总体结果将是对19 q和1 p基因的遗传学和生物学的初步了解，以及对胶质瘤的组织学和基因型联合评估的发展，该评估可能用于对患者进行分层治疗。