Epigenetic silencing of the protocadherin family member PCDH-γ-A11 in astrocytomas

Anke Waha; Stefanie Güntner; Tim Hui Ming Huang; Pearlly S. Yan; Bülent Arslan; Torsten Pietsch; Otmar D. Wiestler; Andreas Waha

doi:10.1593/neo.04490

Epigenetic silencing of the protocadherin family member PCDH-γ-A11 in astrocytomas

Anke Waha
, Stefanie Güntner
, Tim Hui Ming Huang
, Pearlly S. Yan
, Bülent Arslan
, Torsten Pietsch
, Otmar D. Wiestler
, Andreas Waha

Research output: Contribution to journal › Article › peer-review

99 Scopus citations

Abstract

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), and 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.

Original language	English (US)
Pages (from-to)	193-199
Number of pages	7
Journal	Neoplasia
Volume	7
Issue number	3
DOIs	https://doi.org/10.1593/neo.04490
State	Published - Mar 2005
Externally published	Yes

Keywords

Expression
Glioma
Methylation
PCDH-γ-A11
cRT-PCR

ASJC Scopus subject areas

Cancer Research

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10.1593/neo.04490

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@article{20a024836dec45c2aef1da7230849704,

title = "Epigenetic silencing of the protocadherin family member PCDH-γ-A11 in astrocytomas",

abstract = "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), and 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.",

keywords = "Expression, Glioma, Methylation, PCDH-γ-A11, cRT-PCR",

author = "Anke Waha and Stefanie G{\"u}ntner and Huang, \{Tim Hui Ming\} and Yan, \{Pearlly S.\} and B{\"u}lent Arslan and Torsten Pietsch and Wiestler, \{Otmar D.\} and Andreas Waha",

note = "Funding Information: Address all correspondence to: Andreas Waha, PhD, Department of Neuropathology, University of Bonn Medical Center, Sigmund Freud Street 25, Bonn D-53105, Germany. E-mail: [email protected] 1This study was supported by grants from the Deutsche Forschungsgemeinschaft (SFB400C2 to T.P.; SFB400C7 to A.W.), the Lise-Meitner-Habilitation Program (A.W.), National Cancer Institute grants (CA-69065 and CA-86701), and a start-up fund from the Ohio State University Comprehensive Cancer Center (T.H.-M.H and P.S.Y). T. H.-M. Huang is a consultant of Epigenomics, Inc. Received 12 July 2004; Revised 10 August 2004; Accepted 11 August 2004.",

year = "2005",

month = mar,

doi = "10.1593/neo.04490",

language = "English (US)",

volume = "7",

pages = "193--199",

journal = "Neoplasia",

issn = "1522-8002",

publisher = "Elsevier Inc.",

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T1 - Epigenetic silencing of the protocadherin family member PCDH-γ-A11 in astrocytomas

AU - Waha, Anke

AU - Güntner, Stefanie

AU - Huang, Tim Hui Ming

AU - Yan, Pearlly S.

AU - Arslan, Bülent

AU - Pietsch, Torsten

AU - Wiestler, Otmar D.

AU - Waha, Andreas

N1 - Funding Information: Address all correspondence to: Andreas Waha, PhD, Department of Neuropathology, University of Bonn Medical Center, Sigmund Freud Street 25, Bonn D-53105, Germany. E-mail: [email protected] 1This study was supported by grants from the Deutsche Forschungsgemeinschaft (SFB400C2 to T.P.; SFB400C7 to A.W.), the Lise-Meitner-Habilitation Program (A.W.), National Cancer Institute grants (CA-69065 and CA-86701), and a start-up fund from the Ohio State University Comprehensive Cancer Center (T.H.-M.H and P.S.Y). T. H.-M. Huang is a consultant of Epigenomics, Inc. Received 12 July 2004; Revised 10 August 2004; Accepted 11 August 2004.

PY - 2005/3

Y1 - 2005/3

N2 - 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), and 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.

AB - 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), and 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.

KW - Expression

KW - Glioma

KW - Methylation

KW - PCDH-γ-A11

KW - cRT-PCR

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UR - https://www.scopus.com/pages/publications/15744392240#tab=citedBy

U2 - 10.1593/neo.04490

DO - 10.1593/neo.04490

M3 - Article

C2 - 15799819

AN - SCOPUS:15744392240

SN - 1522-8002

VL - 7

SP - 193

EP - 199

JO - Neoplasia

JF - Neoplasia

IS - 3

ER -

Epigenetic silencing of the protocadherin family member PCDH-γ-A11 in astrocytomas

Abstract

Keywords

ASJC Scopus subject areas

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