Article Abstract

Methylation of O6-methylguanine DNA methyltransferase promoter is a predictive biomarker in Chinese melanoma patients treated with alkylating agents

Authors: Jiayi Yu, Huan Yu, Junya Yan, Xiaowen Wu, Lu Yang, Jie Dai, Meng Ma, Huan Tang, Tianxiao Xu, Zhihong Chi, Lu Si, Xinan Sheng, Chuangliang Cui, Jun Guo, Yan Kong

Abstract

Background: The O6-methylguanine-DNA methyltransferase gene (MGMT) promoter methylation status can be used to predict the prognosis of patients with various cancers following treatment with alkylating agents. Moreover, MGMT promoter methylation often coexists with TP53 gene mutation. However, MGMT has not been identified as a biomarker of melanoma. Therefore, this study systematically analyzed the prognostic role of MGMT and the correlation between MGMT methylation and TP53 mutation in non-Caucasian patients with melanoma.
Methods: This study involved tumor samples and clinical data collected from 205 melanoma patients treated with alkylating agents at Peking University Cancer Hospital & Institute. The MGMT promoter methylation and TP53 mutation status were analyzed respectively using methylation-specific polymerase chain reaction and polymerase chain reaction followed by Sanger sequencing. Additionally, MGMT protein expression in tumor samples was assessed via immunohistochemistry.
Results: MGMT promoter methylation was detected in 97 (47%) of the 205 tumor samples, and was significantly associated with a loss of MGMT protein expression (P=0.021). MGMT promoter methylation was also significantly associated with the presence of TP53 mutation (P=0.004). Regarding prognosis, patients without MGMT promoter methylation exhibited worse overall survival outcomes, compared to those with methylation (hazard ratio: 1.443; 95% confidence interval: 0.731–2.342; P=0.015).
Conclusions: MGMT promoter methylation appears to coexist frequently with TP53 mutation. Patients harboring MGMT promoter methylation within tumors may benefit from therapy with alkylating agents.