MOLECULAR CLASSIFICATION OF HUMAN GLIAL TUMORS

本提案中提出的研究旨在提供分子 试剂，以帮助人类神经胶质肿瘤的分类。 星形胶质细胞和少突胶质细胞是主要的神经胶质细胞， 中枢神经系统，并被认为代表了转化 大多数胶质瘤的起源细胞。这些肿瘤的分类是 目前仅基于组织学标准。我们的初步研究 表明编码髓鞘蛋白质的RNA转录物 应该作为少突胶质细胞来源的肿瘤的敏感标志物。 此外，这些研究还表明，人类神经胶质肿瘤的一个子集， 目前被认为是星形胶质细胞起源的可能实际上是 少突胶质细胞起源。我们推测，根据我们对一个 转化的少突胶质细胞系，其表型特性 中枢神经系统神经胶质瘤受肿瘤生长环境的影响， 居住。这些肿瘤的环境由于破坏而改变 血脑屏障和免疫细胞的浸润， 分泌大量的细胞因子我们建议将分子 和组织学表型的人中枢神经系统胶质瘤的程度 淋巴细胞浸润到这些肿瘤和局部浓度 各种细胞因子。反过来，这些结果将与 患者的临床结果。总之，这些研究应该提供 我们的分子试剂，应该有助于分类， 人类神经胶质瘤，使得患病个体的临床过程可以 更准确地预测和设计治疗方案 相应地

The studies presented in this proposal are designed to provide molecular reagents to assist in the classification of human glial tumors. Astrocytes and oligodendrocytes are the predominant glial cells of the central nervous system and are believed to represent the transformed cells of origin in most gliomas. The classification of these tumors is currently based solely on histological criteria. Our preliminary studies indicate that the RNA transcripts that encode the proteins of myelin should serve as sensitive markers of tumors of oligodendrocyte origin. Moreover, these studies also suggest that a subset of human glial tumors currently believed to be of astrocytic origin may actually be of oligodendroglial origin. We speculate, based on our studies with a transformed oligodendrocyte cell line, that the phenotypic properties of CNS glial tumors are influenced by the environment in which these tumors reside. The environment of these tumors is altered due to the disruption of the blood-brain barrier and the infiltration of immune cells, which secrete a multitude of cytokines. We propose to correlate the molecular and histological phenotype of human CNS gliomas with the degree of lymphocyte infiltration into these tumors and the local concentration of various cytokines. In turn, these results will be correlated with the clinical outcome of the patients. Together, these studies should provide us with molecular reagents that should help in the classification of human gliomas such that the clinical course of afflicted individuals may be more accurately predicted and treatment protocols designed accordingly.