Overexpressed Skp2 within 5p amplification detected by array‐based comparative genomic hybridization is associated with poor prognosis of glioblastomas
Overexpressed Skp2 within 5p amplification detected by array‐based comparative genomic hybridization is associated with poor prognosis of glioblastomas
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DOI：
10.1111/j.1349-7006.2005.00099.x
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发表时间：
2005-10
期刊：
影响因子：
5.7
通讯作者：
K. Saigusa;N. Hashimoto;H. Tsuda;S. Yokoi;M. Maruno;T. Yoshimine;M. Aoyagi;Kikuo Ohno;I. Imoto;J. Inazawa
中科院分区：
文献类型：
--
作者：
K. Saigusa;N. Hashimoto;H. Tsuda;S. Yokoi;M. Maruno;T. Yoshimine;M. Aoyagi;Kikuo Ohno;I. Imoto;J. Inazawa
为了更好地了解多形性胶质母细胞瘤 (GBM) 的发病机制并提高预测该疾病患者预后的准确性，我们使用定制的比较基因组杂交阵列对 22 个胶质瘤来源的细胞系中的 DNA 拷贝数畸变进行了全基因组筛查。拷贝数增加经常在 3q、7p、7q、20q、Xp 和 Xq 处检测到，而拷贝数丢失则在 4q、9p、10p、10q、11q、13q、14q、18q 和 22q 处检测到。在几种非随机染色体畸变中，5p DNA 的增益/扩增在 GBM 中从未报道过，在四种细胞系中检测到相对较高的比率（log2 比率 = 0.41-1.19）。在 22 个细胞系中的 4 个中检测到 SKP2（5p 内可能的扩增目标）的扩增和随后的过度表达。我们还通过免疫组织化学研究了原发性 GBM 中该基因产物的表达，结果显示在检查的 35 个肿瘤中，有 11 个肿瘤 (31.4%) 的 Skp2 水平升高。 Skp2 表达升高与总生存期缩短相关（P = 0.001，对数秩检验），尤其是在 65 岁以下的患者中。这些结果表明，通过基因扩增导致的 Skp2 过度表达可能有助于 GBM 的发病机制，并且该蛋白的过量可能是该疾病患者的有用预后工具。(Cancer Sci 2005; 96: 676 – 683)
To better understand the pathogenesis of glioblastoma multiforme (GBM) and to increase the accuracy of predicting outcomes for patients with this disease, we performed genome‐wide screening for DNA copy‐number aberrations in 22 glioma‐derived cell lines using a custom‐made comparative genomic hybridization‐array. Copy‐number gains were frequently detected at 3q, 7p, 7q, 20q, Xp and Xq, and losses at 4q, 9p, 10p, 10q, 11q, 13q, 14q, 18q, and 22q. Among several non‐random chromosomal aberrations, the gain/amplification of DNA at 5p, which has never been reported before in GBM, was detected with a relatively high ratio (log2 ratio = 0.41–1.19) in four cell lines. Amplification and subsequent overexpression of SKP2, a possible target of amplification within 5p, were detected in four of the 22 cell lines. We also investigated the expression of the gene product in primary GBM by immunohistochemistry, which revealed increased levels of Skp2 in 11 of the 35 tumors examined (31.4%). Heightened expression of Skp2 was associated with shorter overall survival (P = 0.001, logrank test), especially in patients younger than 65 years. These results suggest that overexpression of Skp2 through gene amplification may contribute to the pathogenesis of GBM, and that overabundance of the protein might be a useful prognostic tool in patients with this disease.(Cancer Sci 2005; 96: 676 – 683)