Spatiotemporal Evolution of the Primary Glioblastoma Genome
Spatiotemporal Evolution of the Primary Glioblastoma Genome
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DOI：
10.1016/j.ccell.2015.07.013
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发表时间：
2015-09-14
期刊：
影响因子：
50.3
通讯作者：
Nam, Do-Hyun
中科院分区：
文献类型：
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作者：
Kim, Jinkuk;Lee, In-Hee;Nam, Do-Hyun
治疗后肿瘤复发是多形性胶质母细胞瘤(GBM)患者死亡的主要原因。因此，对复发时的进化过程的洞察对于改善患者护理至关重要。在这里，我们描述了我们对38例GBM患者的初发和复发肿瘤标本的基因组分析。驱动因素改变的前景与复发肿瘤的远期外观有关，这表明初始肿瘤的基因组图谱可能会误导远端复发肿瘤的靶向治疗。此外，与IDH1突变的胶质瘤相比，IDH1野生型原发胶质瘤在替莫唑胺(TMZ)治疗后很少发生过度突变，这表明在标准方案下TMZ诱导这些肿瘤过度突变的风险很低。
Tumor recurrence following treatment is the major cause of mortality for glioblastoma multiforme (GBM) patients. Thus, insights on the evolutionary process at recurrence are critical for improved patient care. Here, we describe our genomic analyses of the initial and recurrent tumor specimens from each of 38 GBM patients. A substantial divergence in the landscape of driver alterations was associated with distant appearance of a recurrent tumor from the initial tumor, suggesting that the genomic profile of the initial tumor can mislead targeted therapies for the distally recurred tumor. In addition, in contrast to IDH1-mutated gliomas, IDH1-wild-type primary GBMs rarely developed hypermutation following temozolomide (TMZ) treatment, indicating low risk for TMZ-induced hypermutation for these tumors under the standard regimen.