Epigenetic Silencing of the Protocadherin Family Member PCDH-γ-All in Astrocytomas
In a microarray-based methylation analysis of astrocytomas [World Health Organization (WHO) grade II], we identified a CpG island within the first exon of the protocadherin-γ subfamily A11 (PCDH-γ-A11) gene that showed hypermethylation compared to normal brain tissue. Bisulfite sequencing and combin...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2005-03-01
|
| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S147655860580020X |
| _version_ | 1811263806531174400 |
|---|---|
| author | Anke Waha Stefanie Güntner Tim Hui-Ming Huang Pearlly S. Yan Bülent Arslan Torsten Pietsch Otmar D. Wiestler Andreas Waha |
| author_facet | Anke Waha Stefanie Güntner Tim Hui-Ming Huang Pearlly S. Yan Bülent Arslan Torsten Pietsch Otmar D. Wiestler Andreas Waha |
| author_sort | Anke Waha |
| collection | DOAJ |
| description | In a microarray-based methylation analysis of astrocytomas [World Health Organization (WHO) grade II], we identified a CpG island within the first exon of the protocadherin-γ subfamily A11 (PCDH-γ-A11) gene that showed hypermethylation compared to normal brain tissue. Bisulfite sequencing and combined bisulfite restriction analysis (COBRA) was performed to screen low- and high-grade astrocytomas for the methylation status of this CpG island. Hypermethylation was detected in 30 of 34 (88%) astrocytomas (WHO grades II and III), 20 of 23 (87%) glioblastomas (WHO grade IV), 8 of 8 (100%) glioma cell lines. There was a highly significant correlation (P = .00028) between PCDH-γ-A11 hypermethylation and decreased transcription as determined by competitive reverse transcription polymerase chain reaction in WHO grades II and III astrocytomas. After treatment of glioma cell lines with a demethylating agent, transcription of PCDH-γ-A11 was restored. In summary, we have identified PCDH-γ-A11 as a new target silenced epigenetically in astrocytic gliomas. The inactivation of this cell-cell contact molecule might be involved in the invasive growth of astrocytoma cells into normal brain parenchyma. |
| first_indexed | 2024-04-12T19:53:07Z |
| format | Article |
| id | doaj.art-4c31ce4a72ec4438a9a003c7f210acfb |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-12T19:53:07Z |
| publishDate | 2005-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-4c31ce4a72ec4438a9a003c7f210acfb2022-12-22T03:18:46ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022005-03-017319319910.1593/neo.04490Epigenetic Silencing of the Protocadherin Family Member PCDH-γ-All in AstrocytomasAnke Waha0Stefanie Güntner1Tim Hui-Ming Huang2Pearlly S. Yan3Bülent Arslan4Torsten Pietsch5Otmar D. Wiestler6Andreas Waha7Department of Neuropathology, University of Bonn Medical Center, Bonn, GermanyDepartment of Neuropathology, University of Bonn Medical Center, Bonn, GermanyDivision of Human Cancer Genetics, Department of Molecular Virology, Immunology, Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH, USADivision of Human Cancer Genetics, Department of Molecular Virology, Immunology, Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH, USADepartment of Neuropathology, University of Bonn Medical Center, Bonn, GermanyDepartment of Neuropathology, University of Bonn Medical Center, Bonn, GermanyDepartment of Neuropathology, University of Bonn Medical Center, Bonn, GermanyDepartment of Neuropathology, University of Bonn Medical Center, Bonn, GermanyIn a microarray-based methylation analysis of astrocytomas [World Health Organization (WHO) grade II], we identified a CpG island within the first exon of the protocadherin-γ subfamily A11 (PCDH-γ-A11) gene that showed hypermethylation compared to normal brain tissue. Bisulfite sequencing and combined bisulfite restriction analysis (COBRA) was performed to screen low- and high-grade astrocytomas for the methylation status of this CpG island. Hypermethylation was detected in 30 of 34 (88%) astrocytomas (WHO grades II and III), 20 of 23 (87%) glioblastomas (WHO grade IV), 8 of 8 (100%) glioma cell lines. There was a highly significant correlation (P = .00028) between PCDH-γ-A11 hypermethylation and decreased transcription as determined by competitive reverse transcription polymerase chain reaction in WHO grades II and III astrocytomas. After treatment of glioma cell lines with a demethylating agent, transcription of PCDH-γ-A11 was restored. In summary, we have identified PCDH-γ-A11 as a new target silenced epigenetically in astrocytic gliomas. The inactivation of this cell-cell contact molecule might be involved in the invasive growth of astrocytoma cells into normal brain parenchyma.http://www.sciencedirect.com/science/article/pii/S147655860580020XGliomaPCDH-γ-A11methylationcRT-PCRexpression |
| spellingShingle | Anke Waha Stefanie Güntner Tim Hui-Ming Huang Pearlly S. Yan Bülent Arslan Torsten Pietsch Otmar D. Wiestler Andreas Waha Epigenetic Silencing of the Protocadherin Family Member PCDH-γ-All in Astrocytomas Neoplasia: An International Journal for Oncology Research Glioma PCDH-γ-A11 methylation cRT-PCR expression |
| title | Epigenetic Silencing of the Protocadherin Family Member PCDH-γ-All in Astrocytomas |
| title_full | Epigenetic Silencing of the Protocadherin Family Member PCDH-γ-All in Astrocytomas |
| title_fullStr | Epigenetic Silencing of the Protocadherin Family Member PCDH-γ-All in Astrocytomas |
| title_full_unstemmed | Epigenetic Silencing of the Protocadherin Family Member PCDH-γ-All in Astrocytomas |
| title_short | Epigenetic Silencing of the Protocadherin Family Member PCDH-γ-All in Astrocytomas |
| title_sort | epigenetic silencing of the protocadherin family member pcdh γ all in astrocytomas |
| topic | Glioma PCDH-γ-A11 methylation cRT-PCR expression |
| url | http://www.sciencedirect.com/science/article/pii/S147655860580020X |
| work_keys_str_mv | AT ankewaha epigeneticsilencingoftheprotocadherinfamilymemberpcdhgallinastrocytomas AT stefanieguntner epigeneticsilencingoftheprotocadherinfamilymemberpcdhgallinastrocytomas AT timhuiminghuang epigeneticsilencingoftheprotocadherinfamilymemberpcdhgallinastrocytomas AT pearllysyan epigeneticsilencingoftheprotocadherinfamilymemberpcdhgallinastrocytomas AT bulentarslan epigeneticsilencingoftheprotocadherinfamilymemberpcdhgallinastrocytomas AT torstenpietsch epigeneticsilencingoftheprotocadherinfamilymemberpcdhgallinastrocytomas AT otmardwiestler epigeneticsilencingoftheprotocadherinfamilymemberpcdhgallinastrocytomas AT andreaswaha epigeneticsilencingoftheprotocadherinfamilymemberpcdhgallinastrocytomas |