Advances in Brief Differential Expression of MMAC / PTEN in Glioblastoma Multiforme : Relationship to Localization and Prognosis 1
Advances in Brief Differential Expression of MMAC / PTEN in Glioblastoma Multiforme : Relationship to Localization and Prognosis 1
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发表时间：
1999
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通讯作者：
T. Sano;Huai-En Lin;Xiashan Chen;L. Langford;D. Koul;M. Bondy;K. Hess;J. Myers;Y. Hong;W. Yung;P. Steck
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作者：
T. Sano;Huai-En Lin;Xiashan Chen;L. Langford;D. Koul;M. Bondy;K. Hess;J. Myers;Y. Hong;W. Yung;P. Steck
MMAC/PTEN是一个位于染色体10 q上的肿瘤抑制基因，最近被证明是一种磷脂酰肌醇3，4，5-三磷酸酶，并调节细胞生长和凋亡。在许多人类癌症中，特别是在多形性胶质母细胞瘤（GBM）中，已经报道了MMAC/PTEN的体细胞突变，尽管鉴定的突变的数量（10-35%）显著低于样本中影响MMAC/PTEN基因座的洛的频率（75-95%）。为了进一步研究可能影响MMAC/PTEN的可能改变，我们通过逆转录-PCR检测了一系列胶质瘤中该基因的表达。在GBM与低级别胶质瘤中观察到MMAC/PTEN表达之间的显著差异（P < 0.001），从而模拟了与这些肿瘤中的基因座相关的等位基因缺失的差异。此外，Kaplan-Meier生存曲线，调整年龄和肿瘤分级，显示肿瘤表达高水平的MMAC/PTEN的患者的预后显着更好。此外，GBM的免疫染色显示在约三分之二的肿瘤中几乎没有或没有MMAC/PTEN表达，而其他约三分之一的肿瘤具有显著更高的表达水平。然而，在约三分之二的高表达标本中，观察到异质性表达模式，表明肿瘤内的某些细胞未能表达MMAC/PTEN。这些结果的组合表明，除了影响基因的分子改变之外，MMAC/PTEN的表达改变可能在GBM的进展和患者结局中起重要作用。
MMAC/PTEN, a tumor suppressor gene located on chromosome 10q, has recently been shown to act as a phosphatidylinositol 3,4,5-triphosphate phosphatase and to modulate cell growth and apoptosis. Somatic mutations of MMAC/PTEN have been reported in a number of human cancers, especially in glioblastoma multiforme (GBM), although the number of identified mutations (;10–35%) is significantly lower than the frequency of LOH affecting the MMAC/PTEN locus in the specimens (;75–95%). To further investigate the possible alterations that may affect MMAC/PTEN, we examined the expression of the gene by reverse transcription-PCR in a series of gliomas. A significant difference ( P < 0.001) was observed between the expression of MMAC/PTEN in GBMs versus lower grades of gliomas, thus mimicking the difference in allelic deletion associated with the locus in these tumors. Furthermore, Kaplan-Meier survival plots, adjusted for age and tumor grade, showed a significantly better prognosis for patients whose tumors expressed high levels of MMAC/PTEN. Additionally, immunostaining of GBMs revealed little or no MMAC/PTEN expression in about two-thirds of the tumors, whereas the other approximately one-third of tumors had significantly higher levels of expression. However, in about two-thirds of the high-expressing specimens, a heterogeneous pattern of expression was observed, indicating that certain cells within the tumor failed to express MMAC/PTEN. The combination of these results suggest that, in addition to molecular alterations affecting the gene, altered expression of MMAC/PTEN may play a significant role in the progression of GBM and patient outcome.