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

Jeng Yuan Wu, John Wang, Ji Ching Lai, Ya Wen Cheng, Kun Tu Yeh, Tzu Chin Wu, Chih Yi Chen, Huei Lee

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Background: O6-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. Materials and Methods: 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. Results: 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 highest prevalence of MGMT promoter methylation was found in male nonsmokers followed by male smokers and female nonsmokers. This may be a partial explanation for the reason why male nonsmokers had a higher p53 mutation occurrence than female nonsmokers. Conclusions: MGMT promoter methylation may associate with increased occurrence of p53 mutation including the G:C→A:T transition and other p53 mutation patterns in lung cancer, especially among male nonsmokers.

Original languageEnglish
Pages (from-to)3272-3277
Number of pages6
JournalAnnals of Surgical Oncology
Volume15
Issue number11
DOIs
Publication statusPublished - Nov 2008
Externally publishedYes

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Methyltransferases
Non-Small Cell Lung Carcinoma
Methylation
Histology
Smoking
Mutation
DNA
Neoplasms
Lung
p53 Genes
O-(6)-methylguanine
Squamous Cell Carcinoma
Lung Neoplasms
Adenocarcinoma
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

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. / Wu, Jeng Yuan; Wang, John; Lai, Ji Ching; Cheng, Ya Wen; Yeh, Kun Tu; Wu, Tzu Chin; Chen, Chih Yi; Lee, Huei.

In: Annals of Surgical Oncology, Vol. 15, No. 11, 11.2008, p. 3272-3277.

Research output: Contribution to journalArticle

Wu, Jeng Yuan ; Wang, John ; Lai, Ji Ching ; Cheng, Ya Wen ; Yeh, Kun Tu ; Wu, Tzu Chin ; Chen, Chih Yi ; Lee, Huei. / 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. In: Annals of Surgical Oncology. 2008 ; Vol. 15, No. 11. pp. 3272-3277.
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abstract = "Background: O6-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. Materials and Methods: 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. Results: 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 highest prevalence of MGMT promoter methylation was found in male nonsmokers followed by male smokers and female nonsmokers. This may be a partial explanation for the reason why male nonsmokers had a higher p53 mutation occurrence than female nonsmokers. Conclusions: MGMT promoter methylation may associate with increased occurrence of p53 mutation including the G:C→A:T transition and other p53 mutation patterns in lung cancer, especially among male nonsmokers.",
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T1 - 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

AU - Wu, Jeng Yuan

AU - Wang, John

AU - Lai, Ji Ching

AU - Cheng, Ya Wen

AU - Yeh, Kun Tu

AU - Wu, Tzu Chin

AU - Chen, Chih Yi

AU - Lee, Huei

PY - 2008/11

Y1 - 2008/11

N2 - Background: O6-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. Materials and Methods: 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. Results: 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 highest prevalence of MGMT promoter methylation was found in male nonsmokers followed by male smokers and female nonsmokers. This may be a partial explanation for the reason why male nonsmokers had a higher p53 mutation occurrence than female nonsmokers. Conclusions: MGMT promoter methylation may associate with increased occurrence of p53 mutation including the G:C→A:T transition and other p53 mutation patterns in lung cancer, especially among male nonsmokers.

AB - Background: O6-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. Materials and Methods: 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. Results: 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 highest prevalence of MGMT promoter methylation was found in male nonsmokers followed by male smokers and female nonsmokers. This may be a partial explanation for the reason why male nonsmokers had a higher p53 mutation occurrence than female nonsmokers. Conclusions: MGMT promoter methylation may associate with increased occurrence of p53 mutation including the G:C→A:T transition and other p53 mutation patterns in lung cancer, especially among male nonsmokers.

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