散发性和2型神经纤维瘤病相关神经鞘瘤中的CpG岛甲基化
CpG island methylation in sporadic and neurofibromatis type 2-associated schwannomas.
作者信息
Gonzalez-Gomez Pilar, Bello M Josefa, Alonso M Eva, Lomas Jesus, Arjona Dolores, Campos Jose M de, Vaquero Jesus, Isla Alberto, Lassaletta Luis, Gutierrez Manuel, Sarasa Jose L, Rey Juan A
机构信息
Department of C. Experimental, Laboratorio Oncogenetica Molecular, Hospital Universitario La Paz, Madrid, Spain.
出版信息
Clin Cancer Res. 2003 Nov 15;9(15):5601-6.
PURPOSE
The purpose of this research was to examine the DNA methylation profile of schwannomas.
EXPERIMENTAL DESIGN
We examined the DNA methylation status of 12 tumor-related genes (NF2, RB1, p14(ARF), p16(INK4a), p73, TIMP-3, MGMT, DAPK, THBS1, caspase-8, TP53, and GSTP1) in 44 sporadic and/or NF2-associated schwannomas using methylation-specific PCR.
RESULTS
The most frequently methylated genes were THBS1 (36%), p73 (27%), MGMT (20%), NF2 (18%), and TIMP-3 (18%). The RB1/p16INK4a gene pair displayed aberrant methylayed alleles in 15% of cases, whereas methylation was relatively rare in the other genes (<5%). Methylation was tumor specific because it was absent in two nonneoplastic nerve sheath samples and two nonneoplastic brain samples studied as controls.
CONCLUSIONS
Our findings indicate that aberrant methylation seems to be a mechanism for NF2 gene inactivation, considered an early step in schwannoma tumorigenesis, and as well, aberrant hypermethylation of other tumor-related genes might represent secondary events that also contribute to the development of these tumors.
目的
本研究的目的是检测神经鞘瘤的DNA甲基化谱。
实验设计
我们使用甲基化特异性PCR检测了44例散发性和/或与神经纤维瘤病2型（NF2）相关的神经鞘瘤中12个肿瘤相关基因（NF2、RB1、p14（ARF）、p16（INK4a）、p73、金属蛋白酶组织抑制因子3（TIMP-3）、O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）、死亡相关蛋白激酶（DAPK）、血小板反应蛋白1（THBS1）、半胱天冬酶8（caspase-8）、TP53和谷胱甘肽S-转移酶P1（GSTP1））的DNA甲基化状态。
结果
最常发生甲基化的基因是THBS1（36%）、p73（27%）、MGMT（20%）、NF2（18%）和TIMP-3（18%）。RB1/p16INK4a基因对在15%的病例中显示出异常甲基化等位基因，而其他基因中的甲基化相对少见（<5%）。甲基化具有肿瘤特异性，因为在作为对照研究的两个非肿瘤性神经鞘样本和两个非肿瘤性脑样本中未发现甲基化。
结论
我们的研究结果表明，异常甲基化似乎是NF2基因失活的一种机制，被认为是神经鞘瘤肿瘤发生的早期步骤，此外，其他肿瘤相关基因的异常高甲基化可能代表也有助于这些肿瘤发生发展的继发性事件。
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