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

Simona Ruggieri, Roberto Tamma, Andrea Marzullo, Tiziana Annese, Christian Marinaccio, Mariella Errede, Francesco C. Susca, Rebecca Senetta, Paola Cassoni, Angelo Vacca, Francesco Albano, Chiara Saracino, Angelo Notarangelo, Giorgina Specchia, Domenico Ribatti, Beatrice Nico

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)41-51
Number of pages11
JournalCancer Letters
Volume353
Issue number1
DOIs
Publication statusPublished - 2014

Keywords

  • Bcl-6
  • Brain tumors
  • Glioma
  • Tumor progression

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Ruggieri, S., Tamma, R., Marzullo, A., Annese, T., Marinaccio, C., Errede, M., Susca, F. C., Senetta, R., Cassoni, P., Vacca, A., Albano, F., Saracino, C., Notarangelo, A., Specchia, G., Ribatti, D., & Nico, B. (2014). Translocation of the proto-oncogene Bcl-6 in human glioblastoma multiforme. Cancer Letters, 353(1), 41-51. https://doi.org/10.1016/j.canlet.2014.06.017