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아교모세포종에서 메틸화특이적 중합효소연쇄반응과 Pyrosequencing을 이용한 MGMT 유전자 프로모터 메틸화 분석에 대한 고찰

A Consideration of MGMT Gene Promotor Methylation Analysis for Glioblastoma Using Methylation-Specific Polymerase Chain Reaction and Pyrosequencing

임소덕|고영신|김완섭|한혜승|김욱연|황태숙|이상화|고영초
대한병리학회|2011.02|Journal of Pathology and Translational Medicine|제45권 제1호|pp. 21-29

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키워드

Glioblastoma; MGMT protein
주제분류병리학

초록

Background: O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation is currently the most promising predictive marker for the outcome and benefit from temozolomide treatment in patients with glioblastoma, but there is no consensus on the analysis method for assessing the methylation status in the molecular diagnostic field. The objective of this study was to evaluate methylation-specific polymerase chain reaction (MSP) and pyrosequencing methods for assessing MGMT gene promotor methylation of glioblastoma as well as assessing the MGMT protein expression by immunohistochemistry. Methods: Twenty-seven cases of glioblastoma from the archives at the Department of Pathology Konkuk University Hospital were selected. MGMT promoter methylation was evaluated by MSP and the pyrosequencing methods. The MGMT expression was also measured at the protein level by immunohistochemistry. Results: Overall, MGMT hypermethylation was observed in 44.4% (12/27 cases) of the case of glioblastoma using either MSP or pyrosequencing. The concordant rate was 70.3% (19/27 cases) between MSP and pyrosequencing for MGMT methylation. There was no correlation between MGMT methylation and the protein expression. No significant differences in progression free survival and overall survival were seen between the methylated group and the unmethylated group by using either MSP or pyrosequencing. The status of the MGMT protein expression was correlated with progression free survival (p=0.026). Conclusions: In this study the concordance rate between MSP and the pyrosequencing methods for assessing MGMT gene promotor methylation was relatively low for the cases of glioblastoma. This suggests that more reliable techniques for routine MGMT methylation study of glioblastoma remain to be developed because of quality control and assurance issues.

Abstract

Background: O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation is currently the most promising predictive marker for the outcome and benefit from temozolomide treatment in patients with glioblastoma, but there is no consensus on the analysis method for assessing the methylation status in the molecular diagnostic field. The objective of this study was to evaluate methylation-specific polymerase chain reaction (MSP) and pyrosequencing methods for assessing MGMT gene promotor methylation of glioblastoma as well as assessing the MGMT protein expression by immunohistochemistry. Methods: Twenty-seven cases of glioblastoma from the archives at the Department of Pathology Konkuk University Hospital were selected. MGMT promoter methylation was evaluated by MSP and the pyrosequencing methods. The MGMT expression was also measured at the protein level by immunohistochemistry. Results: Overall, MGMT hypermethylation was observed in 44.4% (12/27 cases) of the case of glioblastoma using either MSP or pyrosequencing. The concordant rate was 70.3% (19/27 cases) between MSP and pyrosequencing for MGMT methylation. There was no correlation between MGMT methylation and the protein expression. No significant differences in progression free survival and overall survival were seen between the methylated group and the unmethylated group by using either MSP or pyrosequencing. The status of the MGMT protein expression was correlated with progression free survival (p=0.026). Conclusions: In this study the concordance rate between MSP and the pyrosequencing methods for assessing MGMT gene promotor methylation was relatively low for the cases of glioblastoma. This suggests that more reliable techniques for routine MGMT methylation study of glioblastoma remain to be developed because of quality control and assurance issues.

참고문헌 (25)

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