Different molecular patterns in glioblastoma multiforme subtypes upon recurrence.
Different molecular patterns in glioblastoma multiforme subtypes upon recurrence.
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DOI：
10.1007/s11060-009-9967-4
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发表时间：
2010-02
影响因子：
3.9
通讯作者：
Schackert, Gabriele
中科院分区：
文献类型：
--
作者：
Martinez, Ramon;Rohde, Veit;Schackert, Gabriele
胶质母细胞瘤的特征之一是其固有的复发倾向。在这一点上，复发性GBM患者的生存时间只有几个月。GBM复发过程的分子基础仍然知之甚少。本研究的目的是研究复发GBM的遗传谱相比，其各自的原发性肿瘤。我们已经包括了20对GBM。在所有的肿瘤样本中，我们分析了p53和PTEN的状态，半定量PCR扩增EGFR和微卫星分析进行了广泛的基因组指纹。在原发性GBM中，我们观察到12例2型GBM、4例1型GBM和4例既未显示p53突变也未显示EGFR扩增的进一步GBM（非1型-非2型GBM）。复发后，我们检测到两种肿瘤进展的分子模式：GBM最初显示1型或2型特征，在复发时保留了它们。而非1型-非2型GBM则具有2型GBM的典型模式，EGFR扩增，无p53突变。复发后新的PTEN突变仅在2型GBM中检测到。在复发的2型GBM中，额外的洛缺失比1型特征更常见。综上所述，我们的研究结果强烈表明，复发的GBM可能会显示两种不同的模式积累的分子变化取决于原始肿瘤的配置文件。本文的在线版本（doi：10.1007/s11060-009-9967-4）包含补充材料，可供授权用户使用。
One of the hallmarks of glioblastoma is its inherent tendency to recur. At this point patients with relapsed GBM show a survival time of only few months. The molecular basis of the recurrence process in GBM is still poorly understood. The aim of the present study was to investigate the genetic profile of relapsed GBM compared to their respective primary tumors. We have included 20 paired GBMs. In all tumor samples, we have analyzed p53 and PTEN status by sequencing analysis, EGFR amplification by semiquantitative PCR and a wide-genome fingerprinting was performed by microsatellite analysis. Among primary GBM, we observed twelve type 2 GBM, four type 1 GBM and four further GBM showing neither p53 mutations nor EGFR amplification (non-type 1–non-type 2 GBM). Upon recurrence, we have detected two molecular patterns of tumor progression: GBM initially showing either type 1 or type 2 profiles conserved them at the time of relapse. In contrast, non-type 1–non-type 2 GBM acquired the typical pattern of type 2 GBM and harbor EGFR amplification without p53 mutation. New PTEN mutations upon relapse were only detected in type 2 GBM. Additional LOH were more frequently identified in relapses of type 2 GBM than in those showing the type 1 signature. Taken together, our results strongly suggest that recurrences of GBM may display two distinct pattern of accumulation of molecular alterations depending on the profile of the original tumor. The online version of this article (doi:10.1007/s11060-009-9967-4) contains supplementary material, which is available to authorized users.
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