MOLECULAR CYTOGENETICS--PEDIATRIC CNS TUMORS

细胞遗传学和分子生物学技术已经使我们对 癌症的生物学基础，特别是儿科肿瘤。 关于小儿中枢神经系统肿瘤的信息， 由于技术问题和联合国获得标本的机会有限。为 基于这些原因，我们提出了一个分子和细胞遗传学评估， 小儿中枢神经系统肿瘤。 在这个程序中，我们将准备核型从一个 儿科脑肿瘤的扩展系列。 我们的研究将包括 肿瘤直接制备物和短期组织培养物的分析 肿瘤标本和外周血。 我们将检查等位基因的丢失 在中枢神经系统肿瘤的17 p上缩小我们提出的包含一个位点的区域， 这对PNETS的发展至关重要。我们将进一步定义和缩小 22q区域暗示含有肿瘤抑制基因座， 横纹肌样瘤或典型的脑畸胎瘤。 易突变“热 将对恶性肿瘤p53基因座中的“斑点”进行测序，以评估 儿童中枢神经系统肿瘤中该位点的突变频率。我们 将开发用于检测i（17 q）和 在临床材料中的单体22，以帮助诊断这些子集 肿瘤。 因此，从我们的研究中鉴定的DNA序列将被应用于 应用PCR技术检测临床标本中的相关异常 分析和间期荧光原位杂交。 最后我们 将这些细胞遗传学和分子检测的结果与 临床结果和免疫表型。这将涉及比较 具有临床特征的细胞遗传学和分子学结果， 专门的免疫组织化学研究。 当我们开始了解 基因组改变的功能后果，通过识别基因， 参与和机制，他们发挥其作用，我们将 能够将这些信息转化为诊断的改善， 疗法

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.