Methylation and expression profiles of MGMT gene in thymic epithelial tumors

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• 作者：Mohamed Mokhtar ; Kazuya Kondo ; Toshiaki Namura ; Abdellah H.K. Ali ; Yui Fujita ; Chikako Takai ; Hiromitsu Takizawa ; Yasushi Nakagawa ; Hiroaki Toba ; Koichiro Kajiura ; Mitsuteru Yoshida ; Gyokei Kawakami ; Shoji Sakiyama ; Akira Tangoku
• 关键词：MGMT ; O6-methylguanine-DNA methyltransferase ; TET ; thymic epithelial tumors ; MSP ; methylation-specific PCR ; MG ; myasthenia gravis ; M ; methylated ; NI ; non-informative case ; U ; unmethylated ; WHO ; World Health Organization ; MI ; methylation index
• 刊名：Lung Cancer
• 出版年：February, 2014
• 年：2014
• 卷：83
• 期：2
• 页码：279-287
• 全文大小：2596 K

文摘

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.