Mutation analysis of B-RAF gene in human gliomas
Mutation analysis of B-RAF gene in human gliomas
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DOI：
10.1007/s00401-004-0936-x
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发表时间：
2005-02-01
影响因子：
12.7
通讯作者：
Reis, RM
中科院分区：
文献类型：
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作者：
Basto, D;Trovisco, V;Reis, RM
RAS/RAF/MEK/ERK激酶通路在活化的生长因子受体的有丝分裂刺激转导中起关键作用，调节细胞增殖、存活和分化。在大约30%的人类肿瘤中发现RAS突变导致这一途径的上调。最近，在很大比例的人类癌症中发现了B-RAF的激活突变。胶质瘤是最常见的原发性中枢神经系统肿瘤，其发生发展的分子机制尚不完全清楚。本研究的目的是阐明82例人类胶质瘤中B-RAF突变的发生率及其与肿瘤进展的可能关系，包括49例星形胶质细胞瘤和33例少突胶质细胞瘤。对B-RAF热点区域，外显子11和15的分析显示，34例胶质母细胞瘤中只有2例（6%）存在B-RAF突变，其余组织学类型中不存在B-RAF突变。这两个突变都位于热点残基600 （V600E）的外显子15，这导致了B-RAF激酶的组成活性。这些数据表明B-RAF的激活突变在胶质瘤中并不常见；然而，当出现时，它们与高度恶性病变有关。
The RAS/RAF/MEK/ERK kinase pathway is pivotal in the transduction of mitogenic stimuli from activated growth factor receptors, which regulates cell proliferation, survival, and differentiation. Up-regulation of this pathway due to RAS mutations is found in approximately 30% of human tumors. Recently, activating mutations of B-RAF were identified in a large proportion of human cancers. Gliomas are the most frequent primary central nervous system tumors and the molecular mechanisms that underlie the development and progression of these tumors are far from being completely understood. The purpose of this study was to clarify the incidence of B-RAF mutations and their possible relation with tumor progression in a series of 82 human gliomas, including 49 astrocytic and 33 oligodendroglial tumors. The analysis of B-RAF hotspot regions, exons 11 and 15, showed presence of B-RAF mutations in only 2 out of 34 (6%) glioblastomas, and absence in the remaining histological types. Both mutations were located in the hotspot residue 600 (V600E) at exon 15, which leads to constitutive B-RAF kinase activity. These data suggest that activating mutations of B-RAF are not a frequent event in gliomas; nevertheless, when present they are associated with high-grade malignant lesions.