Association of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with p53 mutation occurrence in non-small cell lung cancer with different histology, gender, and smoking status

Annals of Surgical Oncology
Jeng-Yuan WuHuei Lee

Abstract

O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been demonstrated to associate with the G:C-->A:T transition mutation in the p53 gene of lung tumors. The purpose of this study is to clarify whether MGMT promoter methylation is not only associated with the shift from the G:C-->A:T mutation in the p53 gene but also whether MGMT increases other mutation patterns in lung tumors. To further verify whether a different prevalence of MGMT promoter methylation is observed in lung tumors with a different tumor histology, gender, and smoking status, 220 lung tumors were collected to evaluate the status of MGMT promoter methylation and p53 mutation using methylation-specific PCR (MSP) and direct sequencing, respectively. The data shows that a higher prevalence of MGMT promoter methylation was observed in tumors with the G:C-->A:T transition or other p53 mutation patterns compared with those with p53 wild-type (P < 0.001 for G:C-->A:T; P = 0.015 for other mutation patterns), and this prevalence was more pronounced in tumors from male than from female patients. MGMT promoter methylation in p53 mutation patterns had a different effect on squamous cell carcinomas (SCC) and adenocarcinomas (ADC). Interestingly, the high...Continue Reading

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