Deletion and aberrant CpG island methylation of Caspase 8 gene in medulloblastoma

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Pilar Gonzalez-Gomez1, M Josefa Bello, M Mar Inda

  • 1Laboratorio de Oncogenética Molecular y Epigenética del Cáncer, Departamento de C. Experimental, Unidad de Investigación, Hospital Universitario La Paz, Paseo Castellana 261, 28046 Madrid, Spain.

Oncology Reports
|August 4, 2004
PubMed

Insights

Aberrant methylation of the Caspase 8 (CASP8) gene is common in medulloblastomas, potentially silencing this tumor suppressor. Genomic deletions may also contribute to CASP8 inactivation in these brain tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Aberrant DNA methylation of gene promoter CpG islands is a known mechanism for tumor development.
  • Medulloblastomas, a common pediatric brain tumor, have been understudied regarding promoter methylation.
  • Caspase 8 (CASP8) is a key mediator of apoptosis, and its silencing can promote tumor growth.

Purpose of the Study:

  • To determine the frequency of aberrant CpG island methylation in the CASP8 gene in medulloblastomas.
  • To investigate potential alternative mechanisms of CASP8 inactivation in these tumors.

Main Methods:

  • Analysis of CASP8 promoter CpG island methylation in 24 medulloblastoma samples (16 pediatric, 8 adult).
  • Use of methylation-specific PCR with primers for methylated and unmethylated alleles.
  • Assessment for genomic alterations in the CASP8 5' flanking region.

Main Results:

  • Complete CASP8 methylation was observed in 62% (15/24) of medulloblastomas.
  • One tumor exhibited hemimethylation of CASP8.
  • Genomic deletion or significant sequence changes in the CASP8 promoter region were suggested in three samples.

Conclusions:

  • CpG island methylation is a frequent mechanism contributing to CASP8 silencing in medulloblastomas.
  • Homozygous deletion or severe promoter sequence alterations represent another potential pathway for CASP8 inactivation in this neoplasm.
  • These findings highlight the importance of CASP8 in medulloblastoma pathogenesis and suggest therapeutic targets.

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