title: Translocation of the proto-oncogene Bcl-6 in human glioblastoma multiforme.
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.
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Ruggieri
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Tamma
authors.affiliation: Department of Emergency and Transplantation, Pathology Unit, University of Bari Medical School, Bari, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Marzullo
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Annese
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Marinaccio
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: Errede
authors.affiliation: Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Francesco C
authors.initials: FC
authors.lastname: Susca
authors.affiliation: Department of Medical Sciences, University of Turin Medical School, Turin, Italy.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Senetta
authors.affiliation: Department of Medical Sciences, University of Turin Medical School, Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cassoni
authors.affiliation: Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Vacca
authors.affiliation: Department of Emergency and Transplantation, Hematology Unit, University of Bari Medical School, Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Albano
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (FG), Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Saracino
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (FG), Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Notarangelo
authors.affiliation: Department of Emergency and Transplantation, Hematology Unit, University of Bari Medical School, Bari, Italy.
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy; National Cancer Institute "Giovanni Paolo II", Bari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy. Electronic address: beatrice.nico@uniba.it.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Nico
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001932:Brain Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D053148:Caspase 3 / Q000032:analysis; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D000090063:Proto-Oncogene Mas; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000032:analysis; D012189:Retrospective Studies; D014178:Translocation, Genetic; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: C084103:BCL6 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Bcl-6; Brain tumors; Glioma; Tumor progression