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Molecular pathology of gliomas

机译:神经胶质瘤的分子病理学

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Gliomas are the most common primary neoplasms of the brain. They are a heterogeneous group of tumours characterized by infiltrative growth, and relative resistance to radiotherapy and chemotherapy. Glioblastomas have complex chromosomal aberrations including amplifications and gains of 7p, 12q13-q21, and chromosome 19, and losses are 10q, 9p, 13q and 22q, whereas the karyotypes of pilocytic astrocytomas show only limited changes. Important genetic aberrations include up-regulation of EGFR and MDM2 function and loss of PTEN function in primary glioblastoma, and up-regulation of PDGFRA and CDK4 function in secondary glioblastomas that arise from a pre-existing lower grade astrocytoma. TP53, CDKNA2 and RB1 functions are often lost in secondary glioblastomas. Amplifications of PDGFRA, KIT and VEGFR2 may also have a role in the genesis of some gliomas. The proteins encoded by these genes have become targets for novel therapies, which include specific inhibitors of the EGFR, KIT, and PDGFR receptor tyrosine kinases. 2006 Elsevier Ltd. All rights reserved.
机译:神经胶质瘤是大脑最常见的原发肿瘤。它们是一组异质性肿瘤,其特征在于浸润性生长以及对放射疗法和化学疗法的相对抗性。胶质母细胞瘤具有复杂的染色体畸变,包括扩增和获得7p,12q13-q21和19号染色体,损失为10q,9p,13q和22q,而毛细胞星形细胞瘤的核型仅显示有限的变化。重要的遗传畸变包括原发性胶质母细胞瘤中EGFR和MDM2功能的上调以及PTEN功能的丧失,以及继发于较低水平星形细胞瘤的继发性胶质母细胞瘤中PDGFRA和CDK4功能的上调。 TP53,CDKNA2和RB1功能通常在继发性胶质母细胞瘤中丧失。 PDGFRA,KIT和VEGFR2的扩增也可能在某些神经胶质瘤的发生中起作用。这些基因编码的蛋白质已成为新型疗法的靶标,其中包括EGFR,KIT和PDGFR受体酪氨酸激酶的特异性抑制剂。 2006 Elsevier Ltd.保留所有权利。

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