Riemenschneider Markus J, Knobbe Christiane B, Reifenberger Guido
Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany.
Int J Cancer. 2003 May 10;104(6):752-7. doi: 10.1002/ijc.11023.
We previously reported on the amplification and overexpression of the mouse double minute 4 homolog gene (MDM4) from 1q32 in a subset of malignant gliomas (Riemenschneider et al., Cancer Res 1999;59:6091-6). More recently, amplification and overexpression of the neighboring contactin 2 gene (CNTN2) was reported in individual malignant gliomas without MDM4 amplification (Rickman et al., Cancer Res 2001;61:2162-8). To address the question of whether 1q32 carries 2 independent amplification targets or a common target other than MDM4 and CNTN2, we analyzed primary malignant gliomas for amplification and overexpression of 17 different genes from this region. Our results indicate a single region of amplification that comprises the genes MDM4, GAC1, PIK3C2B and PEPP3, with only MDM4 amplification being invariably associated with overexpression. CNTN2 was found to be coamplified with MDM4 in 3 malignant gliomas but overexpressed in only 1 of these tumors. No CNTN2 amplification was detected in any of 102 malignant gliomas without MDM4 amplification. Our data therefore corroborate the notion that MDM4 is the main amplification target on 1q32 in malignant gliomas. However, coamplification and overexpression of adjacent genes may provide an additional growth advantage in some malignant gliomas with MDM4 amplification.
我们之前报道过，在一部分恶性胶质瘤中，位于1q32的小鼠双微体4同源基因（MDM4）存在扩增和过表达（里门施奈德等人，《癌症研究》1999年；59:6091 - 6）。最近，有报道称在个别无MDM4扩增的恶性胶质瘤中，相邻的接触蛋白2基因（CNTN2）存在扩增和过表达（里克曼等人，《癌症研究》2001年；61:2162 - 8）。为了探讨1q32携带的是2个独立的扩增靶点，还是除MDM4和CNTN2之外的一个共同靶点，我们分析了原发性恶性胶质瘤中该区域17个不同基因的扩增和过表达情况。我们的结果表明，存在一个单一的扩增区域，该区域包含MDM4、GAC1、PIK3C2B和PEPP3基因，只有MDM4的扩增总是与过表达相关。在3例恶性胶质瘤中发现CNTN2与MDM4共同扩增，但其中只有1例肿瘤中CNTN2过表达。在102例无MDM4扩增的恶性胶质瘤中，未检测到任何CNTN2扩增。因此，我们的数据证实了MDM4是恶性胶质瘤中1q32上主要的扩增靶点这一观点。然而，相邻基因的共同扩增和过表达可能会在一些有MDM4扩增的恶性胶质瘤中提供额外的生长优势。
