ONCOGENE AMPLIFICATION AND EXPRESSION IN NEURAL TUMORS

这项研究的目的是评估癌基因在肺癌中的作用。 神经肿瘤和正常神经细胞中。放大 N-myc癌基因出现在约50%的神经母细胞瘤中 并与不良的临床结果有关，但并不是全部 预后不良的神经母细胞瘤有N-myc 放大。基因扩增的细胞遗传学证据 也在影响大脑的神经肿瘤中发现，例如 髓母细胞瘤与脑原始神经外胚层肿瘤 (Pnet‘s)，但扩增基因的身份尚未确定 下定决心。这项研究将从检查开始 神经母细胞瘤、髓母细胞瘤和大脑PNET N-myc和其他癌基因的定量扩增 肿瘤DNA样本的Southern杂交 癌基因DNA序列。这些肿瘤还将接受以下检查 “Northern”印迹法检测癌基因表达水平。 这将证实被扩增的癌基因也 表达并将确定某些肿瘤是否已增强 不需要扩增的特定癌基因的表达。肿瘤 也将利用原位在单细胞水平上进行研究 杂交。这将检测组织异质性，并将 揭示癌基因细胞的组织学染色特性 扩增或表达。关于癌基因扩增的数据 而表达也将与患者的临床行为有关 肿瘤。有扩增的肿瘤将在 分子水平，以阐明单位的结构 放大。扩增DNA中的遗传重排 癌基因两侧的序列将被检查以寻找证据 剪接位点的特定序列，这可能与 放大过程。最后，癌基因在神经中的作用 将对肿瘤和正常神经细胞进行研究。正常 将对胎儿和成人组织进行癌基因表达检查 并将启动实验来研究生理作用 神经肿瘤细胞系和原代培养细胞中癌基因的研究 神经细胞。这项研究旨在提供更多 遗传标记在儿童精神分裂症临床评估中的应用 神经肿瘤。这也将有助于阐明其发病机制。 这些肿瘤和意志的转化和发展 有助于我们对控制基因的理解 正常神经细胞的增殖和分化。

The goal of this research is to assess the roles of oncogenes in neural tumors and in normal neural cells. Amplification of the oncogene N-myc occurs in approximately 50% of neuroblastomas and is associated with poor clinical outcome, yet not all neuroblastomas with an unfavorable prognosis have N-myc amplification. Cytogenetic evidence of gene amplification has also been found in neural tumors affecting the brain, such as medulloblastomas and cerebral primitive neuroectodermal tumors (PNET's), but the identities of the amplified genes have not been determined. This research will begin by examining neuroblastomas, medulloblastomas, and cerebral PNET's for amplification of N-myc and other oncogenes, by quantitative hybridization of Southern blots of tumor DNA samples with oncogene DNA sequences. The tumors will also be examined by "Northern" blotting to determine levels of oncogenes expression. This will confirm that oncogenes which are amplified are also expressed and will determine whether some tumors have enhanced expression of specific oncogenes without amplification. Tumors will also be studied at the single cell level using in situ hybridization. This will detect tissue heterogeneity and will reveal the histological staining properties of cells with oncogene amplification or expression. The data on oncogene amplification and expression will also be related to the clinical behavior of the tumors. Tumors with amplification will then be studied at the molecular level to elucidate the structure of the units of amplification. Genetic rearrangements within amplified DNA sequences which flank oncogenes will be examined for evidence of specific sequences at splice sites, which may be related to the process of amplification. Finally, the roles of oncogenes in neural tumors and in normal neural cells will be investigated. Normal fetal and adult tissues will be examined for oncogene expression and experiments will be initiated to study the physiological roles of oncogenes in neural tumor cell lines and primary cultures of neural cells. This research is intended to provide additional genetic markers for the clinical assessment of children with neural tumors. It will also help to elucidate the mechanisms of transformation and progression of these tumors and will contribute to our understanding of genes which control the proliferation and differentiation of normal neural cells.