Methylation and expression profiles of MGMT gene in thymic epithelial tumors

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.

Keywords: DNA methylation; Gene silencing; M; MG; MGMT; MI; MSP; NI; O(6)-methylguanine DNA methyltransferase; O(6)-methylguanine-DNA methyltransferase; TET; Thymic carcinoma; Thymic epithelial tumors; Thymoma; U; WHO; World Health Organization; methylated; methylation index; methylation-specific PCR; myasthenia gravis; non-informative case; thymic epithelial tumors; unmethylated.