ONCOGENE AMPLIFICATION AND EXPRESSION IN NEURAL TUMORS

这项研究的目的是评估癌基因在 神经肿瘤和正常神经细胞。 扩增 癌基因N-myc存在于大约50%的神经母细胞瘤中 并与不良临床结局相关，但并非所有 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 也被发现在影响大脑的神经肿瘤中，如 髓母细胞瘤和脑原始神经外胚层肿瘤 (PNET的），但扩增基因的身份还没有得到证实。 测定 这项研究将开始检查 神经母细胞瘤、髓母细胞瘤和脑PNET， N-myc和其他癌基因的扩增，通过定量 肿瘤DNA样品的Southern印迹与 癌基因DNA序列。 肿瘤还将通过以下方式进行检查： “北方”印迹法测定癌基因表达水平。 这将证实，被扩增的癌基因也是 表达，并将决定一些肿瘤是否增强 特定癌基因的表达而不扩增。 肿瘤 也将在单细胞水平上进行研究， 杂交方法 这将检测组织异质性， 显示癌基因表达细胞的组织学染色特性 扩增或表达。 癌基因扩增的数据 并且表达也将与患者的临床行为相关。 肿瘤的 然后，将在 分子水平来阐明 放大 扩增DNA内的遗传重排 将检查癌基因侧翼的序列，以寻找 在剪接位点的特定序列，这可能与 放大的过程。 最后，癌基因在神经系统中的作用 将研究肿瘤和正常神经细胞。 正常 将检查胎儿和成人组织的癌基因表达 实验将开始研究生理作用， 癌基因在神经肿瘤细胞系和原代培养物中的表达 神经细胞 这项研究旨在提供额外的 遗传标记用于儿童的临床评估 神经肿瘤 这也将有助于阐明的机制， 这些肿瘤的转化和进展， 有助于我们理解控制基因的基因， 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.