Amplicons on chromosome 12q13-21 in glioblastoma recurrences
Amplicons on chromosome 12q13-21 in glioblastoma recurrences
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DOI：
10.1002/ijc.24971
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发表时间：
2010-06-01
影响因子：
6.4
通讯作者：
Meese, Eckart
中科院分区：
文献类型：
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作者：
Fischer, Ulrike;Leidinger, Petra;Meese, Eckart
关于人类肿瘤中扩增区域的体内行为，人们知之甚少。第一个证据表明，在复发的肿瘤中，扩增子结构基本保持不变。在这里，我们调查了几个独立的复发性胶质母细胞瘤病例中扩增区域的命运，以及12q13-21扩增与生存的可能联系。我们用阵列-CGH技术分析了胶质母细胞瘤中12q13-21扩增片段的数量和大小及其复发情况。在原发肿瘤中发现的大多数12q13-21扩增片段在随后的复发中丢失。同样，在第一次重复中发现的大多数扩增片段在第二次重复中丢失。复发的剩余扩增片段常扩大或保持大小。然而，由于扩增片段的重现和从头出现，扩增片段的总数在重现中并没有减少。了解肿瘤复发过程中的基因变化，包括基因扩增，将有助于制定合理的治疗策略，以提高患者的存活率。我们发现在缺乏CDK4、CYP27B1、XRCC6BP1(KUB3)或MDM2扩增的胶质母细胞瘤患者中，生存时间显著延长。
There is limited knowledge on the in vivo behavior of amplified regions in human tumors. First evidence indicates that amplicon structures are largely maintained in recurrent tumors. Here, we investigated the fate of amplified regions in several independent cases of recurrent glioblastoma and the possible association of 12q13-21 amplifications and survival. We analyzed 12q13-21 amplicon numbers and sizes in glioblastoma and their recurrences by array-CGH. The majority of the 12q13-21 amplicons found in the original tumor are lost in the subsequent recurrence. Likewise, the majority of the amplicons found in the first recurrence are lost in the second recurrence. The remaining amplicons of recurrences often expanded or were maintained in size. Because of re-emergences and de novo appearances of amplicons, however, the overall number of amplicons did not decrease in the recurrences. Understanding genetic changes including gene amplifications in the development of tumor recurrences will contribute to rational therapeutic strategies for an improved patient survival. We recognized a significant longer survival time in glioblastoma patients that lack amplifications of either CDK4, CYP27B1, XRCC6BP1 (KUB3), or MDM2.