MOLECULAR CYTOGENETICS--PEDIATRIC CNS TUMORS

分子细胞遗传学--儿童中枢神经系统肿瘤

• 批准号: 2092098
• 负责人: JACLYN A BIEGEL
• 金额: $ 22.16万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-01-13 至 1996-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2092098
• 关键词: Wilms' tumor; adolescence (12-20); alleles; biopsy; brain neoplasms; child (0-11); chromosome aberrations; chromosome disorders; cytogenetics; genetic mapping; human tissue; immunocytochemistry; in situ hybridization; karyotype; middle childhood (6-11); neoplasm /cancer diagnosis; neoplasm /cancer genetics; nucleic acid sequence; pediatric neoplasm /cancer; polymerase chain reaction; rhabdomyosarcoma; teratoma; tissue /cell culture; tumor suppressor genes

Cytogenetic and molecular techniques have advanced our knowledge of the biologic basis of cancer, particularly in the pediatric neoplasms. Information regarding pediatric tumors of the central nervous system has been limited due to technical problems and United access to specimens. For these reasons we propose a molecular and cytogenetic evaluation of pediatric CNS tumors. In this program, we will prepare karyotypes from an extended series of pediatric brain tumors. Our studies will include analysis of direct preparations from tumors, and short term tissue culture of tumor specimens and peripheral blood. We will examine loss of alleles on 17p in CNS tumors to narrow the region which we propose contains a locus critical to the development of PNETS. We will further define and narrow the region of 22q implicated as containing a tumor suppressor locus for rhabdoid or a typical teratoid tumors of the brain. Mutation-prone "hot spots" in the p53 locus of malignant tumors will be sequenced to assess the frequency of mutations in this locus in pediatric tumors of the CNS. We will develop sequence-based diagnostic assays for detection of i(17q) and monosomy 22 in clinical material to aid in the diagnosis of these subsets of tumors. Thus, DNA sequences identified from our studies will be applied to detection of the relevant abnormality in clinical samples by PCR analysis and interphase fluorescence in situ hybridization. Finally, we will correlate the findings of these cytogenetic and molecular assays with clinical outcome and immunophenotyping. This will involve comparisons of the cytogenetic and molecular findings with clinical characteristics and specialized immunohistochemical studies. As we begin to understand the functional consequences of genomic alterations, by identifying the genes involved and the mechanisms by which they exert their effect, we will be able to translate this information into improvements in diagnosis and therapy.

细胞遗传学和分子技术已经提高了我们对 癌症的生物基础，特别是在小儿肿瘤中。 有关中枢神经系统小儿肿瘤的信息 由于技术问题和联合访问标本而受到限制。为了 这些原因我们提出了分子和细胞遗传学评估 小儿中枢神经系统肿瘤。 在此程序中，我们将从一个 扩展的一系列小儿脑肿瘤。 我们的研究将包括 分析肿瘤的直接制剂和短期组织培养 肿瘤标本和外周血。 我们将检查等位基因的损失 在中枢神经系统肿瘤中的17便士以缩小我们建议的区域的区域 对PNET的发展至关重要。我们将进一步定义和缩小 22q的区域牵涉到包含肿瘤抑制基因座的区域 大脑的横纹肌或典型的霉菌肿瘤。 容易突变的“热 斑点“在恶性肿瘤的p53基因座中将进行测序以评估 中枢神经系统小儿肿瘤中该基因座突变的频率。我们 将开发基于序列的诊断测定法以检测I（17Q）和 临床材料中的单肌22，以帮助诊断这些子集 肿瘤。 因此，将应用从我们的研究中确定的DNA序列 检测PCR临床样本中相关异常 分析和相间荧光原位杂交。 最后，我们 将将这些细胞遗传学和分子测定的发现与 临床结果和免疫表型。这将涉及比较 具有临床特征和的细胞遗传学和分子发现 专门的免疫组织化学研究。 当我们开始理解 通过识别基因的基因组改变的功能后果 参与以及它们发挥作用的机制，我们将是 能够将这些信息转化为诊断和 治疗。