Alonso M Eva, Bello M Josefa, Arjona Dolores, Martinez-Glez Victor, de Campos Jose M, Isla Alberto, Kusak Elena, Vaquero Jesús, Gutierrez Manuel, Sarasa Jose L, Rey Juan A
Department of Experimental Surgery, Molecular, Oncogenetics Laboratory, Research Unit, Hospital Universitario La Paz, Madrid, Spain.
Am J Clin Pathol. 2005 Jun;123(6):900-6. doi: 10.1309/448Y-RWNC-43TE-32KQ.
Proto-oncogene amplification is an important alteration that is present in about 45% to 50% of high-grade human gliomas. We studied this mechanism in 8 genes (cyclin-dependent kinase-4 [CDK4], MDM2, MDM4, renin-angiotensin system-1, ELF3, GAC1, human epidermal growth factor receptor-2, and platelet-derived growth factor receptor-A gene) in a series of 40 oligodendrogliomas (World Health Organization (WHO) grade II, 21; WHO grade III, 13; and WHO grade II-III oligoastrocytomas, 6) using real-time quantitative polymerase chain reaction. Amplification of at least 1 of these genes was detected in 58% of samples (23/40). By histopathologic grade, 67% of grade II oligodendrogliomas (14/21), 46% of grade III anaplastic oligodendrogliomas (6/13), and 50% of mixed oligoastrocytomas (3/6) were positive for amplification of at least 1 gene. CDK4, MDM2, and GAC1 were the most frequently involved genes (12/40 [30%], 12/40 [30%], and 13/40 [33%], respectively). Our findings demonstrate gene amplification in low-grade samples indicating that it is an important alteration in the early steps of oligodendroglioma development and, therefore, might be considered a molecular mechanism leading to malignant progression toward anaplastic forms.
原癌基因扩增是一种重要的改变，约45%至50%的高级别人类胶质瘤中存在这种改变。我们使用实时定量聚合酶链反应，对一系列40例少突胶质细胞瘤（世界卫生组织（WHO）二级，21例；WHO三级，13例；以及WHO二级至三级的少突星形细胞瘤，6例）中的8个基因（细胞周期蛋白依赖性激酶4 [CDK4]、MDM2、MDM4、肾素-血管紧张素系统-1、ELF3、GAC1、人表皮生长因子受体-2和血小板衍生生长因子受体-A基因）进行了研究。在58%的样本（23/40）中检测到这些基因中至少有1个基因发生扩增。按组织病理学分级，67%的二级少突胶质细胞瘤（14/21）、46%的三级间变性少突胶质细胞瘤（6/13）和50%的混合性少突星形细胞瘤（3/6）至少有1个基因扩增呈阳性。CDK4、MDM2和GAC1是最常受累的基因（分别为12/40 [30%]、12/40 [30%]和13/40 [33%]）。我们的研究结果表明低级别样本中存在基因扩增，这表明它是少突胶质细胞瘤发展早期阶段的一种重要改变，因此，可能被认为是导致向间变性形式恶性进展的分子机制。
