Translocation of the proto-oncogene Bcl-6 in human glioblastoma multiforme

Cancer Lett. 2014 Oct 10;353(1):41-51. doi: 10.1016/j.canlet.2014.06.017. Epub 2014 Jul 17.

Abstract

Bcl-6 translocation is a genetic alteration that is commonly detected in Primary Central Nervous System Lymphoma. The role of this protein in cerebral tumors is unclear. In this study we investigated Bcl-6 translocation and its transcriptional and translational levels in formalin-fixed, paraffin-embedded cerebral tissue sections from glioblastoma (GBM), low-grade glioma (Astrocytoma grade II and III), and meningioma patients, and correlated them with apoptotic processes and p53 and caspase-3 expression. The results showed a frequency of 36.6% of Bcl-6 translocation in GBM patients and a decreased expression in low-grade glioma patients, correlated with the severity of the disease. Bcl-6 translocation induced an overexpression of both Bcl-6 protein and messenger in GBM, inhibiting apoptotic processes and caspases 3 expression. On the contrary, in low-grade gliomas and meningiomas Bcl-6 expression was reduced, resulting in an increase of apoptotic processes. Finally, p53 expression levels in brain tumors were comparable to Bcl-6 levels. Overall, these data demonstrate, for the first time, that the Bcl-6 gene translocates in GBM patients and that its translocation and expression are correlated with apoptosis inhibition, indicating a key role for this gene in the control of cellular proliferation. This study offers further insights into glioblastoma biology, and supports Bcl-6 as a new diagnostic marker to evaluate the disease severity.

Keywords: Bcl-6; Brain tumors; Glioma; Tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / chemistry
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Caspase 3 / analysis
  • Cell Proliferation
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / chemistry
  • Glioblastoma / genetics*
  • Glioblastoma / pathology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Messenger / analysis
  • Retrospective Studies
  • Translocation, Genetic*
  • Tumor Suppressor Protein p53 / analysis

Substances

  • BCL6 protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Messenger
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • CASP3 protein, human
  • Caspase 3