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MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations
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| Zeitschriftentitel: | International Journal of Cancer |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , |
| In: | International Journal of Cancer, 131, 2012, 5, S. 1104-1113 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
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| Schlagwörter: |
| author_facet |
Mulholland, Shani Pearson, Danita M. Hamoudi, Rifat A. Malley, Deborah S. Smith, Caroline M. Weaver, Jamie M.J. Jones, David T.W. Kocialkowski, Sylvia Bäcklund, L. Magnus Collins, V. Peter Ichimura, Koichi Mulholland, Shani Pearson, Danita M. Hamoudi, Rifat A. Malley, Deborah S. Smith, Caroline M. Weaver, Jamie M.J. Jones, David T.W. Kocialkowski, Sylvia Bäcklund, L. Magnus Collins, V. Peter Ichimura, Koichi |
|---|---|
| author |
Mulholland, Shani Pearson, Danita M. Hamoudi, Rifat A. Malley, Deborah S. Smith, Caroline M. Weaver, Jamie M.J. Jones, David T.W. Kocialkowski, Sylvia Bäcklund, L. Magnus Collins, V. Peter Ichimura, Koichi |
| spellingShingle |
Mulholland, Shani Pearson, Danita M. Hamoudi, Rifat A. Malley, Deborah S. Smith, Caroline M. Weaver, Jamie M.J. Jones, David T.W. Kocialkowski, Sylvia Bäcklund, L. Magnus Collins, V. Peter Ichimura, Koichi International Journal of Cancer MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations Cancer Research Oncology |
| author_sort |
mulholland, shani |
| spelling |
Mulholland, Shani Pearson, Danita M. Hamoudi, Rifat A. Malley, Deborah S. Smith, Caroline M. Weaver, Jamie M.J. Jones, David T.W. Kocialkowski, Sylvia Bäcklund, L. Magnus Collins, V. Peter Ichimura, Koichi 0020-7136 1097-0215 Wiley Cancer Research Oncology http://dx.doi.org/10.1002/ijc.26499 <jats:title>Abstract</jats:title><jats:p>We have previously identified a region containing 16 CpGs within the <jats:italic>MGMT</jats:italic> CpG islands which is critical for the transcriptional control of <jats:italic>MGMT</jats:italic> (Malley, Acta Neuropathol 2011). To investigate the patterns and incidence of <jats:italic>MGMT</jats:italic> methylation in astrocytic and oligodendroglial tumors, we quantitatively assessed methylation at these 16 CpGs using bisulfite modification followed by pyrosequencing of 362 gliomas not treated with temozolomide, and correlated the findings with previously identified patterns of genetic abnormalities, patients' age and survival. The <jats:italic>MGMT</jats:italic> gene was considered to be methylated when the mean methylation of the 16 CpGs was 10% or higher. This cut‐off value distinguished diffuse astrocytomas with high and low <jats:italic>MGMT</jats:italic> expression. Within each tumor type, the patterns of methylation were highly variable and also highly heterogeneous across the 16 CpGs. A high incidence of <jats:italic>MGMT</jats:italic> methylation was observed in all subtypes of gliomas included in this study. Among a subset of 97 tumors where conventional methylation‐specific PCR (MSP) was also applied, methylation was detected by both methods in 54 tumors, while the pyrosequencing results identified a further 17 tumors. No additional cases were found using MSP alone, indicating that pyrosequencing is a robust method for methylation analysis. All tumors with <jats:italic>IDH1/IDH2</jats:italic> mutations except two had <jats:italic>MGMT</jats:italic> methylation, while there were many tumors with <jats:italic>MGMT</jats:italic> methylation, particularly primary glioblastomas, which had no mutations of <jats:italic>IDH1/2</jats:italic>. We suggest that <jats:italic>MGMT</jats:italic> methylation may be one of the earliest events in the development of astrocytic and oligodendroglial tumors.</jats:p> <i>MGMT</i> CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with <i>IDH1</i> or <i>IDH2</i> mutations International Journal of Cancer |
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| title |
MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations |
| title_unstemmed |
MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations |
| title_full |
MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations |
| title_fullStr |
MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations |
| title_full_unstemmed |
MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations |
| title_short |
MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations |
| title_sort |
<i>mgmt</i> cpg island is invariably methylated in adult astrocytic and oligodendroglial tumors with <i>idh1</i> or <i>idh2</i> mutations |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1002/ijc.26499 |
| publishDate |
2012 |
| physical |
1104-1113 |
| description |
<jats:title>Abstract</jats:title><jats:p>We have previously identified a region containing 16 CpGs within the <jats:italic>MGMT</jats:italic> CpG islands which is critical for the transcriptional control of <jats:italic>MGMT</jats:italic> (Malley, Acta Neuropathol 2011). To investigate the patterns and incidence of <jats:italic>MGMT</jats:italic> methylation in astrocytic and oligodendroglial tumors, we quantitatively assessed methylation at these 16 CpGs using bisulfite modification followed by pyrosequencing of 362 gliomas not treated with temozolomide, and correlated the findings with previously identified patterns of genetic abnormalities, patients' age and survival. The <jats:italic>MGMT</jats:italic> gene was considered to be methylated when the mean methylation of the 16 CpGs was 10% or higher. This cut‐off value distinguished diffuse astrocytomas with high and low <jats:italic>MGMT</jats:italic> expression. Within each tumor type, the patterns of methylation were highly variable and also highly heterogeneous across the 16 CpGs. A high incidence of <jats:italic>MGMT</jats:italic> methylation was observed in all subtypes of gliomas included in this study. Among a subset of 97 tumors where conventional methylation‐specific PCR (MSP) was also applied, methylation was detected by both methods in 54 tumors, while the pyrosequencing results identified a further 17 tumors. No additional cases were found using MSP alone, indicating that pyrosequencing is a robust method for methylation analysis. All tumors with <jats:italic>IDH1/IDH2</jats:italic> mutations except two had <jats:italic>MGMT</jats:italic> methylation, while there were many tumors with <jats:italic>MGMT</jats:italic> methylation, particularly primary glioblastomas, which had no mutations of <jats:italic>IDH1/2</jats:italic>. We suggest that <jats:italic>MGMT</jats:italic> methylation may be one of the earliest events in the development of astrocytic and oligodendroglial tumors.</jats:p> |
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| author | Mulholland, Shani, Pearson, Danita M., Hamoudi, Rifat A., Malley, Deborah S., Smith, Caroline M., Weaver, Jamie M.J., Jones, David T.W., Kocialkowski, Sylvia, Bäcklund, L. Magnus, Collins, V. Peter, Ichimura, Koichi |
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| description | <jats:title>Abstract</jats:title><jats:p>We have previously identified a region containing 16 CpGs within the <jats:italic>MGMT</jats:italic> CpG islands which is critical for the transcriptional control of <jats:italic>MGMT</jats:italic> (Malley, Acta Neuropathol 2011). To investigate the patterns and incidence of <jats:italic>MGMT</jats:italic> methylation in astrocytic and oligodendroglial tumors, we quantitatively assessed methylation at these 16 CpGs using bisulfite modification followed by pyrosequencing of 362 gliomas not treated with temozolomide, and correlated the findings with previously identified patterns of genetic abnormalities, patients' age and survival. The <jats:italic>MGMT</jats:italic> gene was considered to be methylated when the mean methylation of the 16 CpGs was 10% or higher. This cut‐off value distinguished diffuse astrocytomas with high and low <jats:italic>MGMT</jats:italic> expression. Within each tumor type, the patterns of methylation were highly variable and also highly heterogeneous across the 16 CpGs. A high incidence of <jats:italic>MGMT</jats:italic> methylation was observed in all subtypes of gliomas included in this study. Among a subset of 97 tumors where conventional methylation‐specific PCR (MSP) was also applied, methylation was detected by both methods in 54 tumors, while the pyrosequencing results identified a further 17 tumors. No additional cases were found using MSP alone, indicating that pyrosequencing is a robust method for methylation analysis. All tumors with <jats:italic>IDH1/IDH2</jats:italic> mutations except two had <jats:italic>MGMT</jats:italic> methylation, while there were many tumors with <jats:italic>MGMT</jats:italic> methylation, particularly primary glioblastomas, which had no mutations of <jats:italic>IDH1/2</jats:italic>. We suggest that <jats:italic>MGMT</jats:italic> methylation may be one of the earliest events in the development of astrocytic and oligodendroglial tumors.</jats:p> |
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| spelling | Mulholland, Shani Pearson, Danita M. Hamoudi, Rifat A. Malley, Deborah S. Smith, Caroline M. Weaver, Jamie M.J. Jones, David T.W. Kocialkowski, Sylvia Bäcklund, L. Magnus Collins, V. Peter Ichimura, Koichi 0020-7136 1097-0215 Wiley Cancer Research Oncology http://dx.doi.org/10.1002/ijc.26499 <jats:title>Abstract</jats:title><jats:p>We have previously identified a region containing 16 CpGs within the <jats:italic>MGMT</jats:italic> CpG islands which is critical for the transcriptional control of <jats:italic>MGMT</jats:italic> (Malley, Acta Neuropathol 2011). To investigate the patterns and incidence of <jats:italic>MGMT</jats:italic> methylation in astrocytic and oligodendroglial tumors, we quantitatively assessed methylation at these 16 CpGs using bisulfite modification followed by pyrosequencing of 362 gliomas not treated with temozolomide, and correlated the findings with previously identified patterns of genetic abnormalities, patients' age and survival. The <jats:italic>MGMT</jats:italic> gene was considered to be methylated when the mean methylation of the 16 CpGs was 10% or higher. This cut‐off value distinguished diffuse astrocytomas with high and low <jats:italic>MGMT</jats:italic> expression. Within each tumor type, the patterns of methylation were highly variable and also highly heterogeneous across the 16 CpGs. A high incidence of <jats:italic>MGMT</jats:italic> methylation was observed in all subtypes of gliomas included in this study. Among a subset of 97 tumors where conventional methylation‐specific PCR (MSP) was also applied, methylation was detected by both methods in 54 tumors, while the pyrosequencing results identified a further 17 tumors. No additional cases were found using MSP alone, indicating that pyrosequencing is a robust method for methylation analysis. All tumors with <jats:italic>IDH1/IDH2</jats:italic> mutations except two had <jats:italic>MGMT</jats:italic> methylation, while there were many tumors with <jats:italic>MGMT</jats:italic> methylation, particularly primary glioblastomas, which had no mutations of <jats:italic>IDH1/2</jats:italic>. We suggest that <jats:italic>MGMT</jats:italic> methylation may be one of the earliest events in the development of astrocytic and oligodendroglial tumors.</jats:p> <i>MGMT</i> CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with <i>IDH1</i> or <i>IDH2</i> mutations International Journal of Cancer |
| spellingShingle | Mulholland, Shani, Pearson, Danita M., Hamoudi, Rifat A., Malley, Deborah S., Smith, Caroline M., Weaver, Jamie M.J., Jones, David T.W., Kocialkowski, Sylvia, Bäcklund, L. Magnus, Collins, V. Peter, Ichimura, Koichi, International Journal of Cancer, MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations, Cancer Research, Oncology |
| title | MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations |
| title_full | MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations |
| title_fullStr | MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations |
| title_full_unstemmed | MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations |
| title_short | MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations |
| title_sort | <i>mgmt</i> cpg island is invariably methylated in adult astrocytic and oligodendroglial tumors with <i>idh1</i> or <i>idh2</i> mutations |
| title_unstemmed | MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1002/ijc.26499 |