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Promoter methylation pattern of caspase-8, P16INK4A, MGMT, TIMP-3, and E-cadherin in medulloblastoma

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Pathology & Oncology Research

Abstract

Methylation of promoter regions of CpG-rich sites is an important mechanism for silencing of tumor suppressor genes (TSG). To evaluate the role of tumor suppressor genes caspase-8 (CASP8), TIMP-3, E-cadherin (CDH1), p16INK4A, and MGMT in medulloblastoma tumorigenesis, 51 medulloblastomas (46 primary tumor specimens, 5 cell lines) were screened for methylation of promoter linked CpG-islands. For CASP8, we examined the 5′ UTR region that has been shown to be associated with expression of CASP8. As detected by methylation specific PCR, methylation rate was low for TIMP-3 (3% of tumor samples; 1/5 cell lines), for MGMT (0% of tumor samples; 1/5 cell lines), for p16INK4A (2% of tumor samples; 2/5 cell lines) and for CDH1 (8% of tumor samples; 1/4 cell lines). CASP8, however, was methylated in 90% of tumor samples and 4/5 cell lines examined. Screening other tumor entities for CASP8 methylation, we found a similarly high level in 6 neuroblastoma cell lines in contrast to 5 osteosarcoma-, 4 Ewing’s sarcoma-and 6 non-embryonic tumor cell lines without any increased promoter methylation. From our results we conclude that methylation of the CASP8 5′ UTR region may play a role in inactivation of CASP8 in neural crest tumors.

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Abbreviations

CASP8:

caspase-8

MGMT:

O6-methylguanine-DNA-methyl-transferase

PNET:

primitive neuroectodermal tumor

TIMP-3:

tissue inhibitor of met alloproteinase 3

TRAIL:

TNF-related apoptosis inducing ligand

TSG:

tumor suppressor gene

UTR:

untranslated region

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Authors and Affiliations

  1. Department of Molecular Pathology, Institute of Pathology, Tübingen, University Hospital Gießen, Gießen, Germany

    Martin Ebinger

  2. Cnopf’sche Kinderklinik, Nürnberg, University Hospital Gießen, Gießen, Germany

    Leonore Senf & Wolfram Scheurlen

  3. Zentrum für Kinderheilkunde und Jugendmedizin, University Hospital Gießen, Gießen, Germany

    Olga Wachowski

Authors
  1. Martin Ebinger
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  2. Leonore Senf
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  3. Olga Wachowski
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  4. Wolfram Scheurlen
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Correspondence to Wolfram Scheurlen.

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Ebinger, M., Senf, L., Wachowski, O. et al. Promoter methylation pattern of caspase-8, P16INK4A, MGMT, TIMP-3, and E-cadherin in medulloblastoma. Pathol. Oncol. Res. 10, 17–21 (2004). https://doi.org/10.1007/BF02893403

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  • DOI: https://doi.org/10.1007/BF02893403

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