O6-Methylguanine DNA Methyltransferase (Mgmt) Promoter Methylation in Primitive Neuroectodermal Brain Tumor (Pnet) Correlates with MGMT RNA Expression and Sensitivity of PNET Cells to Temozolomide : PM.002
Details
Serval ID
serval:BIB_C40D723917A6
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
O6-Methylguanine DNA Methyltransferase (Mgmt) Promoter Methylation in Primitive Neuroectodermal Brain Tumor (Pnet) Correlates with MGMT RNA Expression and Sensitivity of PNET Cells to Temozolomide : PM.002
Title of the conference
41st Annual Conference of the International Society of Paediatric Oncology
Address
Sao Paulo, Brazil, October 5-9, 2009
ISBN
1545-5009
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
53
Series
Pediatric Blood & Cancer
Pages
825
Language
english
Notes
Purpose: Medulloblastomas (MB) are the most common malignant brain tumors in childhood. Alkylator based drugs are effective in the treatment of patients with MB. In several tumors, including malignant glioma, elevated O6-methylguanine-DNA methyltransferase (MGMT) expression levels or lack of MGMT promoter methylation have been found to be associated with resistance to alkylating chemotherapeutic agents such as temozolomide (TMZ). In this study, we examined the MGMT status of MB and central nervous system primitive neuroectodermal tumor (PNET) cells and two large sets of primary MB.We then investigated the response of MB/PNET cells to
TMZ and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU).
Method: Please refer to results section.
Results: In 7 MB/PNET cell lines investigated, MGMT promoter methylation was
detected only in D425 human MB cells as assayed by the qualitative
methylation-specific PCR and the more quantitative pyrosequencing assay. In D425 human MB cells, MGMT mRNA and protein expression was clearly lower when compared with the MGMT expression in the other MB/PNET cell lines.
Pyrosequencing of 67 formalin-fixed paraffin-embedded primary MB revealed a low percentage of MGMT methylation (range, 3.7-92.0%, mean: 13.25%, median: 10.76%). Percentage of MGMT methylation and MGMT mRNA expression as determined by quantitative RT-PCR correlated inversely (n¼46; Pearson correlation r2¼0.14, p¼0.01). In MB/PNET cells, sensitivity towards TMZ and CCNU correlated with MGMT methylation and MGMT mRNA expression. We then analyzed MGMT mRNA expression in a second set of 47 formalin-fixed paraffin-embedded tumor samples from well-documented patients treated within the prospective randomized multicenter trial HIT'91. No association was found between MGMT mRNA expression and progression-free or overall survival outcome.
Conclusion: Our in vitro findings indicate that MGMT methylation and/or mRNA
expression can predict response to alkylating agents. However, the percentage of MGMT methylation is relatively low in childhood MB, indicating resistance to alkylating agents mediated by MGMT in most tumors.
TMZ and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU).
Method: Please refer to results section.
Results: In 7 MB/PNET cell lines investigated, MGMT promoter methylation was
detected only in D425 human MB cells as assayed by the qualitative
methylation-specific PCR and the more quantitative pyrosequencing assay. In D425 human MB cells, MGMT mRNA and protein expression was clearly lower when compared with the MGMT expression in the other MB/PNET cell lines.
Pyrosequencing of 67 formalin-fixed paraffin-embedded primary MB revealed a low percentage of MGMT methylation (range, 3.7-92.0%, mean: 13.25%, median: 10.76%). Percentage of MGMT methylation and MGMT mRNA expression as determined by quantitative RT-PCR correlated inversely (n¼46; Pearson correlation r2¼0.14, p¼0.01). In MB/PNET cells, sensitivity towards TMZ and CCNU correlated with MGMT methylation and MGMT mRNA expression. We then analyzed MGMT mRNA expression in a second set of 47 formalin-fixed paraffin-embedded tumor samples from well-documented patients treated within the prospective randomized multicenter trial HIT'91. No association was found between MGMT mRNA expression and progression-free or overall survival outcome.
Conclusion: Our in vitro findings indicate that MGMT methylation and/or mRNA
expression can predict response to alkylating agents. However, the percentage of MGMT methylation is relatively low in childhood MB, indicating resistance to alkylating agents mediated by MGMT in most tumors.
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08/12/2009 15:44
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20/08/2019 15:39
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