脑胶质瘤相关基因的DNA甲基化及其意义

国际肿瘤学杂志››2015,Vol. 42››Issue (10): 762-765.doi:10.3760/cma.j.issn.1673-422X.2015.10.012

脑胶质瘤相关基因的DNA甲基化及其意义

闫晓光,化定超,郭庚,鲁晨阳

030001 太原，山西医科大学第二临床医学院（闫晓光、化定超、鲁晨阳）；山西医科大学第一医院神经外科（郭庚）

出版日期:2015-10-08发布日期:2015-09-08
通讯作者:郭庚 E-mail:guogeng973@163.com
基金资助:

国家自然科学基金（81201991）；中国博士后科学基金（2015M571068）；山西省高等学校创新人才支持计划(晋教科［2013］8号)；山西省卫生厅科研课题（201301066）

DNA methylation of glioma related gene and its significance

Yan Xiaoguang, Hua Dingchao, Guo Geng, Lu Chenyang

Second Clinical Medical College, Shanxi Medical University, Taiyuan 030001, China

Online:2015-10-08Published:2015-09-08
Contact:Guo Geng E-mail:guogeng973@163.com

摘要/Abstract

摘要：DNA甲基化与脑胶质瘤的发生发展关系密切。胶质瘤中的许多基因如DNA修复基因、细胞周期调控基因、细胞凋亡相关基因、肿瘤抑制基因、侵袭相关基因等的启动子区胞嘧啶磷酸鸟嘌呤位点富集区（CpG岛）存在高甲基化。胶质瘤多个基因的甲基化谱和特异分子标志物的发现有助于胶质瘤的病理分级、早期诊断、判断预后。同时，DNA甲基化具有可逆转的特性，这可能为胶质瘤的治疗提供新的途径。

闫晓光,化定超,郭庚,鲁晨阳. 脑胶质瘤相关基因的DNA甲基化及其意义[J]. 国际肿瘤学杂志, 2015, 42(10): 762-765.

Yan Xiaoguang, Hua Dingchao, Guo Geng, Lu Chenyang. DNA methylation of glioma related gene and its significance[J]. Journal of International Oncology, 2015, 42(10): 762-765.

［1］ Bicker J, Alves G, Fortuna A, et al. Bloodbrain barrier models and their relevance for a successful development of CNS drug delivery systems: a review［J］. Eur J Pharm Biopharm, 2014, 87(3): 409-432. ［2］董方, 薛金才, 王小虎. 恶性脑胶质瘤的综合治疗［J］. 国际肿瘤学杂志, 2014, 41(11): 816-820. ［3］ Westphal M, Lamszus K. The neurobiology of gliomas: from cell biology to the development of therapeutic approaches［J］. Nat Rev Neurosci, 2011, 12(9): 495-508. ［4］ Kreth S, Thon N, Kreth FW. Epigenetics in human gliomas［J］. Cancer Lett, 2014, 342(2): 185-192. ［5］ Kanemoto M, Shirahata M, Nakauma A, et al. Prognostic prediction of glioblastoma by quantitative assessment of the methylation status of the entire MGMT promoter region［J］. BMC Cancer, 2014, 14: 641. ［6］ Cohen KJ, Pollack IF, Zhou T, et al. Temozolomide in the treatment of highgrade gliomas in children: a report from the Children′s Oncology Group［J］. Neuro Oncol, 2011, 13(3): 317-323. ［7］ Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase Ⅲ study: 5year analysis of the EORTCNCIC trial［J］. Lancet Oncol, 2009, 10(5): 459-466. ［8］ Kreth S, Thon N, Eigenbrod S, et al. OmethylguanineDNA methyltransferase (MGMT) mRNA expression predicts outcome in malignant glioma independent of MGMT promoter methylation［J］. PLoS One, 2011, 6(2): e17156. ［9］ FerrerLuna R, Núez L, Piquer J, et al. Wholegenomic survey of oligodendroglial tumors: correlation between allelic imbalances and gene expression profiles［J］. J Neurooncol, 2011, 103(1): 71-85. ［10］ Feng J, Kim ST, Liu W, et al. An integrated analysis of germline and somatic, genetic and epigenetic alterations at 9p21.3 in glioblastoma［J］. Cancer, 2012, 118(1): 232-240. ［11］ Sibin MK, Bhat DI, Narasingarao KV, et al. CDKN2A (p16) mRNA decreased expression is a marker of poor prognosis in malignant highgrade glioma［J］. Tumour Biol, 2015, In press. ［12］ Kuo LT, Tsai SY, Chang CC, et al. Genetic and epigenetic alterations in primaryprogressive paired oligodendroglial tumors［J］. PLoS One, 2013, 8(6): e67139. ［13］ Zheng S, Houseman EA, Morrison Z, et al. DNA hypermethylation profiles associated with glioma subtypes and EZH2 and IGFBP2 mRNA expression［J］. Neuro Oncol, 2011, 13(3): 280-289. ［14］ Ramirez JL, Taron M, Balaa C, et al. Serum DNA as a tool for cancer patient management［J］. Rocz Akad Med Bialymst, 2003, 48: 34-41. ［15］ Hesson L, Bièche I, Krex D, et al. Frequent epigenetic inactivation of RASSF1A and BLU genes located within the critical 3p21.3 region in gliomas［J］. Oncogene, 2004, 23(13): 2408-2419. ［16］ MajchrzakCelińska A, Paluszczak J, Szalata M, et al. The methylation of a panel of genes differentiates lowgrade from highgrade gliomas［J］. Tumour Biol, 2015, 36(5): 3831-3841. ［17］ Kosla K, Pluciennik E, Kurzyk A, et al. Molecular analysis of WWOX expression correlation with proliferation and apoptosis in glioblastoma multiforme［J］. J Neurooncol, 2011, 101(2): 207-213. ［18］ Agnihotri S, Wolf A, Munoz DM, et al. A GATA4regulated tumor suppressor network represses formation of malignant human astrocytomas［J］. J Exp Med, 2011, 208(4): 689-702. ［19］ Vaitkiené P, Skiriuté D, Skauminas K, et al. GATA4 and DcR1 methylation in glioblastomas［J］. Diagn Pathol, 2013, 8: 7. ［20］ Skiriuté D, Steponaitis G, Vaitkiené P, et al. Glioma malignancydependent NDRG2 gene methylation and downregulation correlates with poor patient outcome［J］. J Cancer, 2014, 5(6): 446-456. ［21］ Jiang Z, Zhou W, Li XG, et al. The methylation analysis of EMP3 and PCDHgammaA11 gene in human glioma［J］. Zhonghua Wai Ke Za Zhi, 2010, 48(4): 300-304. ［22］ Lindemann C, Hackmann O, Delic S, et al. SOCS3 promoter methylation is mutually exclusive to EGFR amplification in gliomas and promotes glioma cell invasion through STAT3 and FAK activation［J］. Acta Neuropathol, 2011, 122(2): 241-251. ［23］ Alonso MM, DiezValle R, Manterola L, et al. Genetic and epigenetic modifications of Sox2 contribute to the invasive phenotype of malignant gliomas［J］. PLoS One, 2011, 6(11): e26740. ［24］ Liu BL, Cheng JX, Zhang W, et al. Quantitative detection of multiple gene promoter hypermethylation in tumor tissue, serum, and cerebrospinal fluid predicts prognosis of malignant gliomas［J］. Neuro Oncol, 2010, 12(6): 540-548. ［25］ Kelly TK, De Carvalho DD, Jones PA. Epigenetic modifications as therapeutic targets［J］. Nat Biotechnol, 2010, 28(10): 1069-1078.

[1]	刘萍萍, 何学芳, 张翼, 杨旭, 张珊珊, 季一飞.原发性脑胶质瘤患者术后复发危险因素及预测模型构建[J]. 国际肿瘤学杂志, 2024, 51(4): 193-197.
[2]	肖楠, 孙鹏飞.氧化应激在胶质瘤放化疗敏感性中的研究进展[J]. 国际肿瘤学杂志, 2022, 49(6): 357-361.
[3]	孔春禹, 孙鹏飞.SLC7A11与胶质瘤[J]. 国际肿瘤学杂志, 2022, 49(10): 604-607.
[4]	郭世豪, 任叶青, 郭庚.脑胶质瘤血管生成拟态分子机制[J]. 国际肿瘤学杂志, 2021, 48(6): 362-365.
[5]	王宪伟, 史美燕, 王凤芹, 齐福, 王朝喆, 周飞.TSA上调miR-4298靶向抑制PADI4表达在诱导U251细胞凋亡中的作用[J]. 国际肿瘤学杂志, 2021, 48(4): 193-199.
[6]	邓波儿, 孔为民.子宫内膜癌的表观遗传学研究进展[J]. 国际肿瘤学杂志, 2021, 48(3): 184-188.
[7]	何苗, 范奎, 曹芳.表观遗传与肺癌耐药[J]. 国际肿瘤学杂志, 2021, 48(10): 622-626.
[8]	张雯, 胡伟国, 宋启斌.3D-ASL与DCE-MRI在脑胶质瘤复发与放射性脑坏死鉴别诊断中的价值[J]. 国际肿瘤学杂志, 2021, 48(10): 631-634.
[9]	桑莹冰, 梁俊琴.皮肤鳞状细胞癌表观遗传学发病机制[J]. 国际肿瘤学杂志, 2020, 47(9): 569-572.
[10]	赵聪选, 于韬.胶质瘤相关基因的挖掘及预测[J]. 国际肿瘤学杂志, 2020, 47(5): 293-296.
[11]	南阳, 钟跃.长非编码RNA在神经胶质瘤研究中的新进展[J]. 国际肿瘤学杂志, 2020, 47(2): 98-102.
[12]	张雯, 宋启斌, 胡伟国.多模态磁共振成像在脑胶质瘤中的临床应用[J]. 国际肿瘤学杂志, 2020, 47(11): 686-690.
[13]	陈亮, 秦军, 雷军荣, 刘俊, 王璐.miR-1254通过靶向CSF-1抑制胶质瘤细胞的增殖和侵袭能力[J]. 国际肿瘤学杂志, 2020, 47(10): 577-584.
[14]	张千慧, 张洋, 宿伟鹏, 张宋安, 刘攀, 赵化荣.LSD1、MGMT和Ki-67在高级别胶质瘤中的表达及对预后的影响[J]. 国际肿瘤学杂志, 2019, 46(9): 519-525.
[15]	衣琳, 邱实.紫草素抗胶质瘤效应及其作用机制[J]. 国际肿瘤学杂志, 2019, 46(8): 489-491.