Comprehensive analysis of genomic alterations in gliosarcoma and its two tissue components
Comprehensive analysis of genomic alterations in gliosarcoma and its two tissue components
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DOI：
10.1002/gcc.10087
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发表时间：
2002-08-01
影响因子：
3.7
通讯作者：
Weber, RG
中科院分区：
文献类型：
--
作者：
Actor, B;Cobbers, JMJL;Weber, RG
胶质肉瘤是多形性胶质母细胞瘤的一种变体，其特征在于表现出胶质瘤或肉瘤分化的两种成分。我们研究了 38 种胶质肉瘤的肿瘤抑制基因和原癌基因的畸变，这些基因在胶质母细胞瘤中通常发生改变。分别在 11% (4/35)、8% (3/38)、8% (3/38) 和 3% (1/35) 的肿瘤中发现 CDK4、MDM2、EGFR 和 PDGFRA 扩增。 38 例胶质肉瘤中的 9 例 (24%) 携带 TP53 突变。在 45% (9/20) 的研究肿瘤中发现了 PTEN 突变。通过比较基因组杂交（CGH）分析了二十个神经胶质肉瘤。常见的染色体失衡包括 7 号染色体（15/20；75%）、X 号染色体（4/20；20%）、9q 和 20q 染色体（3/20，各 15%）； 10 号和 9p 号染色体（7/20，各 35%）和 13q 号染色体（3/20，15%）丢失。通过 CGH 将 5 个不同的高水平扩增映射到 4q12-21（1 例）、6p21（1 例）、7p12（2 例）、近端 12q（4 例）和 14q32（1 例）。 Southern 印迹和/或差异 PCR 分析鉴定了各个肿瘤中 PDGFRA (4q 12)、CCND3 (6l 1)、EGFR (7p12)、CDK4 (12q14) 和/或 MDM2 (12q14.3-q15) 和 AKT1 (14q32.3) 的扩增。经过显微解剖和通用 DNA 扩增后，通过 CGH 对八种神经胶质肉瘤的神经胶质瘤和肉瘤成分进行单独分析，结果显示这两种成分共享检测到的染色体失衡的 57%。综上所述，我们的数据表明胶质肉瘤的基因组变化与胶质母细胞瘤中发现的基因组变化非常相似。然而，胶质肉瘤中涉及不平衡的染色体数量显着低于胶质母细胞瘤，表明胶质肉瘤的基因组稳定性更高。此外，我们进一步支持了这样的假设：神经胶质瘤和肉瘤成分源自单个前体细胞克隆，在肿瘤进化过程中进展为具有不同形态特征的亚克隆。根据我们的数据，近端 12q 基因的获得/扩增可能促进肉瘤表型的发展。 (C) 2002 Wiley-Liss, Inc.
Gliosarcoma is a variant of glioblastoma multiforme characterized by two components displaying gliomatous or sarcomatous differentiation. We investigated 38 gliosarcomas for aberrations of tumor-suppressor genes and proto-oncogenes that are commonly altered in glioblastomas. Amplification of CDK4, MDM2, EGFR, and PDGFRA were found in 11% (4/35), 8% (3/38), 8% (3/38), and 3% (1/35) of the tumors, respectively. Nine of 38 gliosarcomas (24%) carried TP53 mutations. PTEN mutations were identified in 45% (9/20) of the investigated tumors. Twenty gliosarcomas were analyzed by comparative genomic hybridization (CGH). Chromosomal imbalances commonly detected were gains on chromosomes 7 (15/20; 75%), X (4/20; 20%), 9q, and 20q (3/20, 15% each); and losses on chromosomes 10 and 9p (7/20, 35% each), and 13q (3/20, 15%). Five different high-level amplifications were mapped to 4q12-21 (1 case), 6p21 (1 case), 7p12 (2 cases), proximal 12q (4 cases), and 14q32 (1 case) by CGH. Southern blot and/or differential PCR analyses identified amplification of PDGFRA (4q 12), CCND3 (6l 1), EGFR (7p12), CDK4 (12q14) and/or MDM2 (12q14.3-q15), and AKT1 (14q32.3) in the respective tumors. Separate analysis of the gliomatous and sarcomatous components of eight gliosarcomas by CGH after microdissection and universal DNA amplification revealed that both components shared 57% of the chromosomal imbalances detected. Taken together, our data indicate that the genomic changes in gliosarcomas closely resemble those found in glioblastomas. However, the number of chromosomes involved in imbalances in gliosarcomas was significantly lower than that in glioblastomas, indicating a higher genomic stability in gliosarcomas. In addition, we provide further support for the hypothesis that the gliomatous and sarcomatous components are derived from a single precursor cell clone, which progressed into subclones with distinct morphological features during tumor evolution. According to our data, gain/amplification of genes on proximal 12q may facilitate the development of a sarcomatous phenotype. (C) 2002 Wiley-Liss, Inc.