Weber R G, Rieger J, Naumann U, Lichter P, Weller M
Abteilung Organisation komplexer Genome, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Int J Cancer. 2001 Jan 15;91(2):213-8. doi: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1036>3.3.co;2-d.
The median survival for human malignant glioma patients treated with neurosurgery and postoperative radiotherapy does not exceed one year. Only a minority of patients benefit from adjuvant chemotherapy. It was the aim of our study to determine which genomic alterations in malignant gliomas modulate the sensitivity to chemotherapy or cytotoxic cytokines such as CD95 ligand (CD95L) or Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL). Therefore, we analyzed 12 human malignant glioma cell lines for chromosomal gains and losses by comparative genomic hybridization (CGH). The gains most commonly identified were on chromosomes 7q, 19, 1, and 20q, whereas the most frequent losses were on 13q, 11q, 18q, and 4q. By comparison with previously published data on this panel of glioma cell lines1112, we defined candidate regions which may carry genes responsible for sensitivity to chemotherapy or cytotoxic cytokines. All but one of the chromosomal regions associated with response to chemotherapy, i.e. 1p12, 3p21, 11p11.2-p13, 12q23, 17p11. 2-p13, were different from those associated with response to cytotoxic cytokines, i.e. lp12, 1q22, 12q12-q21. Genomic regions known to harbor major candidate genes, including genes encoding death ligands, death receptors, caspases and BCL-2 family proteins, were not found to be imbalanced. In addition, we identified 5q13-q14, 5q34, 10p11.2, 9q21-q34 as genomic regions associated with the proliferative activity of malignant glioma cell lines. Cell lines with gain on proximal 5q, where CCNB1 and CCNH reside, showed an increased growth rate, suggesting that cyclins activating cdc2, the dominant G2/M phase kinase, may play a role in glioma tumorigenes.
接受神经外科手术和术后放疗的人类恶性胶质瘤患者的中位生存期不超过一年。只有少数患者能从辅助化疗中获益。我们研究的目的是确定恶性胶质瘤中的哪些基因组改变会调节对化疗或细胞毒性细胞因子（如CD95配体（CD95L）或Apo2L/肿瘤坏死因子相关凋亡诱导配体（Apo2L/TRAIL））的敏感性。因此，我们通过比较基因组杂交（CGH）分析了12种人类恶性胶质瘤细胞系的染色体增减情况。最常见的增益发生在7q、19、1和20q染色体上，而最常见的缺失发生在13q、11q、18q和4q染色体上。通过与先前发表的关于该胶质瘤细胞系面板的数据进行比较，我们定义了可能携带负责化疗或细胞毒性细胞因子敏感性的基因的候选区域。与化疗反应相关的所有染色体区域（即1p12、3p21、11p11.2 - p13、12q23、17p11.2 - p13），除了一个之外，都与细胞毒性细胞因子反应相关的区域（即lp12、1q22、12q12 - q21）不同。未发现已知含有主要候选基因的基因组区域存在失衡，这些基因包括编码死亡配体、死亡受体、半胱天冬酶和BCL - 2家族蛋白的基因。此外，我们确定5q13 - q14、5q34、10p11.2、9q21 - q34为与恶性胶质瘤细胞系增殖活性相关的基因组区域。在近端5q有增益的细胞系，即CCNB1和CCNH所在的区域，显示出生长速率增加，这表明激活cdc2（主要的G2/M期激酶）的细胞周期蛋白可能在胶质瘤肿瘤发生中起作用。
