Journal of Pathology and Translational Medicine

Original Articles

MGMT Gene Promoter Methylation Analysis by Pyrosequencing of Brain Tumour.: Young Zoon Kim, Young Jin Song, Ki Uk Kim, Dae Cheol Kim; Korean J Pathol. 2011;45(5):455-462.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.455

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BACKGROUND
The aim of this study was to determine whether pyrosequencing (PSQ) might be useful to achieve O6-methyl guanine methyltransferase (MGMT) promoter methylation using 1- to 13-year-old archival tissues as a clinical biomarker in routine practice.
METHODS
The study included 141 formalin-fixed paraffin-embedded (FFPE) glial tumors from the archives of the Pathology Department from 1997-2010.
RESULTS
The average percentage of methylation (MP) of the 141 cases was 14.0+/-16.8%, and methylated cases were 32.3+/-14.9%. The average MP of each year did not show a linear increasing or decreasing pattern according to the age of the FFPE block (p=0.771). The average MP of methylated glioblastomas was 35.8+/-14.7%, 31.8+/-15.5% for anaplastic astrocytomas, and 22.4+/-15.1% for astrocytoma. A tendency was observed toward an increasing pattern of average MP with World Health Organization (WHO) grade (p=0.063) in astrocytic tumors. A correlation was observed between average MP and WHO grade (p=0.038) and a bimodal distribution was observed between the methylated and unmethylated cases, using a 9% cut-off value (p<0.001).
CONCLUSIONS
The results showed that a quantitative approach for MGMT promoter methylation yielded a 100% success rate for FFPE tissues from archives. PSQ can be used in a retrospective trial, but the cut-off value and calculation method should be further validated.

Citations

Citations to this article as recorded by

CDKN2A Homozygous Deletion Is a Stronger Predictor of Outcome than IDH1/2-Mutation in CNS WHO Grade 4 Gliomas
Sang Hyuk Lee, Tae Gyu Kim, Kyeong Hwa Ryu, Seok Hyun Kim, Young Zoon Kim
Biomedicines.2024; 12(10): 2256. CrossRef
Immunohistochemical Classification of Primary and Secondary Glioblastomas
Kyu Sang Lee, Gheeyoung Choe, Kyung Han Nam, An Na Seo, Sumi Yun, Kyung Ju Kim, Hwa Jin Cho, Sung Hye Park
Korean Journal of Pathology.2013; 47(6): 541. CrossRef

A Consideration of MGMT Gene Promotor Methylation Analysis for Glioblastoma Using Methylation-Specific Polymerase Chain Reaction and Pyrosequencing.: Sang Hwa Lee, Tae Sook Hwang, Young Cho Koh, Wook Youn Kim, Hye Seung Han, Wan Seop Kim, Young Sin Ko, So Dug Lim; Korean J Pathol. 2011;45(1):21-29.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.21

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Abstract PDF

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.

Citations

Citations to this article as recorded by

Prognostic Role of Methylation Status of theMGMTPromoter Determined Quantitatively by Pyrosequencing in Glioblastoma Patients
Dae Cheol Kim, Ki Uk Kim, Young Zoon Kim
Journal of Korean Neurosurgical Society.2016; 59(1): 26. CrossRef
Distinct genetic alterations in pediatric glioblastomas
Sun-ju Byeon, Jae Kyung Myung, Se Hoon Kim, Seung-Ki Kim, Ji Hoon Phi, Sung-Hye Park
Child's Nervous System.2012; 28(7): 1025. CrossRef
MGMTGene Promoter Methylation Analysis by Pyrosequencing of Brain Tumour
Young Zoon Kim, Young Jin Song, Ki Uk Kim, Dae Cheol Kim
The Korean Journal of Pathology.2011; 45(5): 455. CrossRef

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