Real-time quantitative PCR analysis of pediatric ependymomas identifies novel candidate genes including TPR at 1q25 and CHIBBY at 22q12-q13
Real-time quantitative PCR analysis of pediatric ependymomas identifies novel candidate genes including TPR at 1q25 and CHIBBY at 22q12-q13
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DOI：
10.1002/gcc.20607
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发表时间：
2008-11-01
影响因子：
3.7
通讯作者：
Warr, Tracy J.
中科院分区：
文献类型：
--
作者：
Karakoula, Katherine;Suarez-Merino, Blanca;Warr, Tracy J.
22 号染色体的丢失和 1q 的增加是室管膜瘤中最常见的基因组畸变，表明映射到这些区域的基因在其发病机制中至关重要。使用实时定量 PCR，我们测量了 47 个小儿颅内室管膜瘤中映射到 22q12.3-q13.33 的 10 个基因和 1q21-32 上的 10 个基因的相对拷贝数。 81% 的病例检测到 22 上的一个或多个基因缺失，其中 22q12-q13.1 处的 RAC2 和 C22ORF2 在室管膜瘤样本中最常缺失，分别为 38% 和 32%。定量 PCR 与甲基化特异性 PCR 和亚硫酸氢盐测序相结合的分析揭示了 C22ORF2 转录失活率很高（>60% 室管膜瘤），表明其在儿科室管膜瘤发展中的潜在重要性。 61% 的病例中检测到 Iq 上至少一个基因的相对拷贝数增加，而 1q25 的 TPR 在 38% 的病例中显示出相对拷贝数增加。患者年龄被认为是一个显着的不良预后因素，因为在 2 岁的患者中观察到总生存时间显着缩短 (P = 0.0056)。 22q13 处 RAC2 缺失或 1q25 处 TPR 扩增与这些年轻患者的总生存期较短显着相关（分别为 P = 0.0492 和 P = < 0.0001）。这项研究确定了 1q 和 22q 内的候选靶基因，这些基因在颅内小儿室管膜瘤的发病机制中可能很重要。 (c) 2008 年 Wiley-Liss, Inc.
Loss of chromosome 22 and gain of 1q are the most frequent genomic aberrations in ependymomas, indicating that genes mapping to these regions are critical in their pathogenesis. Using real-time quantitative PCR, we measured relative copy numbers of 10 genes mapping to 22q12.3-q13.33 and 10 genes at 1q21-32 in a series of 47 pediatric intracranial ependymomas. Loss of one or more of the genes on 22 was detected in 81% of cases, with RAC2 and C22ORF2 at 22q12-q13.1 being deleted most frequently in 38% and 32% of ependymoma samples, respectively. Combined analysis of quantitative-PCR with methylation-specific PCR and bisulphite sequencing revealed a high rate (>60% ependymoma) of transcriptional inactivation of C22ORF2, indicating its potential importance in the development of pediatric ependynnomas. Increase of relative copy numbers of at least one gene on Iq were detected in 61% of cases, with TPR at 1q25 displaying relative copy number gains in 38% of cases. Patient age was identified as a significant adverse prognostic factor as a significantly shorter overall survival time (P = 0.0056) was observed in patients 2 years of age. Loss of RAC2 at 22q13 or amplification of TPR at 1q25 was significantly associated with shorter overall survival in these younger patients (P = 0.0492 and P = < 0.0001, respectively). This study identifies candidate target genes within 1q and 22q that are potentially important in the pathogenesis of intracranial pediatric ependymomas. (c) 2008 Wiley-Liss, Inc.