Estiar Mehrdad Asghari, Javan Firouzeh, Zekri Ali, Mehrazin Masoud, Mehdipour Parvin
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.
Cancer Biomark. 2017 Jul 4;19(3):341-351. doi: 10.3233/CBM-160546.
Astrocytoma and meningioma are the most common primary brain tumors. MYCN as a member of MYC proto-oncogenes has recently appeared as an attractive therapeutic target. Functions of MYCN are critical for growth of nervous system and neural differentiation.
We examined MYCN amplification and protein expression in astrocytoma and meningioma cases.
In this study, we used real-time PCR, FISH assay and flowcytometry to analyze DNA amplification and protein expression of MYCN.
Among 30 samples of brain tumor, 14 cases (46.6%) revealed MYCN amplification. High-protein expression of MYCN was also observed in 43.3% of patients. There was a significant correlation between MYCN gene amplification and protein expression (r= 0.523; p= 0.003), interestingly five case showed discrepancy between the gene amplification and protein expression. Although MYCN amplification fails to show correlation with poor prognosis (p= 0.305), protein high-expression of MYCN significantly reduce disease-free survival (p= 0.019).
Our results challenge the concept of the neural specificity of MYCN by demonstrating contribution of MYCN in meningioma. Moreover, this study highlights the importance of research at both level of DNA and protein, to determine the biological functions and medical impacts of MYCN.
星形细胞瘤和脑膜瘤是最常见的原发性脑肿瘤。MYCN作为MYC原癌基因家族的一员,最近已成为一个有吸引力的治疗靶点。MYCN的功能对神经系统的生长和神经分化至关重要。
我们检测了星形细胞瘤和脑膜瘤病例中MYCN的扩增及蛋白表达情况。
在本研究中,我们使用实时PCR、荧光原位杂交(FISH)检测和流式细胞术分析MYCN的DNA扩增及蛋白表达。
在30例脑肿瘤样本中,14例(46.6%)显示有MYCN扩增。43.3%的患者也观察到MYCN的高蛋白表达。MYCN基因扩增与蛋白表达之间存在显著相关性(r = 0.523;p = 0.003),有趣的是,有5例在基因扩增和蛋白表达之间存在差异。虽然MYCN扩增与预后不良无相关性(p = 0.305),但MYCN蛋白高表达显著降低无病生存期(p = 0.019)。
我们的结果通过证明MYCN在脑膜瘤中的作用,对MYCN的神经特异性概念提出了挑战。此外,本研究强调了在DNA和蛋白两个层面进行研究以确定MYCN的生物学功能和医学影响的重要性。