MGMT 基因在胸腺瘤中的甲基化和表达谱。

Methylation and expression profiles of MGMT gene in thymic epithelial tumors.

机构信息

Department of Oncological Medical Services, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan; Department of Oncological Surgery, Minia Oncology Institute, Minia, Egypt.

Department of Oncological Medical Services, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.

出版信息

Lung Cancer. 2014 Feb;83(2):279-87. doi: 10.1016/j.lungcan.2013.12.004. Epub 2013 Dec 21.

DOI:10.1016/j.lungcan.2013.12.004

PMID:24388682

Abstract

OBJECTIVES

A key challenge in diagnosis and treatment of thymic epithelial tumors (TET) is in improving our understanding of the genetic and epigenetic changes of these relatively rare tumors.

METHODS

Methylation specific PCR (MSP) and immunohistochemistry were applied to 66 TET to profile the methylation status of DNA repair gene O6-methylguanine DNA methyltransferase (MGMT) and its protein expression in TET to clarify the association between MGMT status and clinicopathological features, response to chemotherapy and overall survival.

RESULTS

MGMT methylation was significantly more frequent in thymic carcinoma than in thymoma (17/23, 74% versus 13/44, 29%; P<0.001). Loss of expression of MGMT protein was significantly more frequent in thymic carcinoma than in thymoma (20/23, 87% versus 10/44, 23%; P<0.0001). There is a significant correlation between of MGMT methylation and loss of its protein expression (P<0.0003). MGMT methylation and loss of expression were significantly more frequent in advanced thymic epithelial tumors (III/IV) than in early tumors (I/II).

CONCLUSION

MGMT methylation plays a soul role in development of TET, especially in thymic carcinoma. Therefore, translation of our results from basic molecular research to clinical practice may have important implication for considering MGMT methylation as a marker and a target of future therapies in TET.

摘要

目的

胸腺上皮肿瘤（TET）诊断和治疗的一个关键挑战是提高我们对这些相对罕见肿瘤遗传和表观遗传变化的理解。

方法

应用甲基化特异性 PCR（MSP）和免疫组织化学方法对 66 例 TET 进行检测，以分析 DNA 修复基因 O6-甲基鸟嘌呤 DNA 甲基转移酶（MGMT）的甲基化状态及其在 TET 中的蛋白表达，以阐明 MGMT 状态与临床病理特征、化疗反应和总生存之间的关系。

结果

MGMT 甲基化在胸腺癌中明显比胸腺瘤更常见（17/23，74%对 13/44，29%；P<0.001）。MGMT 蛋白表达缺失在胸腺癌中明显比胸腺瘤更常见（20/23，87%对 10/44，23%；P<0.0001）。MGMT 甲基化和蛋白表达缺失之间存在显著相关性（P<0.0003）。MGMT 甲基化和蛋白表达缺失在晚期 TET（III/IV）中明显比早期肿瘤（I/II）更常见。