Article
Far Upstream Element [FUSE] Binding Protein 1 (FUBP1) expression is associated with increased proliferative activity, p53 accumulation and the presence of mutations in human gliomas
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Authors
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Peter Baumgarten
- Goethe University Frankfurt, Edinger Institute (Neurological Institute), Frankfurt, Germany
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Patrick N. Harter
- Goethe University Frankfurt, Edinger Institute (Neurological Institute), Frankfurt, Germany
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Martje Tönjes
- Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany
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David Capper
- Institute of Neuropathology, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Anna-Eva Blank
- Goethe University Frankfurt, Edinger Institute (Neurological Institute), Frankfurt, Germany
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Bettina Schwamb
- Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus, Frankfurt, Germany
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Uta Rabenhorst
- Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus, Frankfurt, Germany
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Donat Kögel
- Experimental Neurosurgery, Center for Neurology and Neurosurgery, Frankfurt, Germany
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Ralf J. Rieker
- Institute of Pathology, Erlangen, Germany
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Karl-Heinz Plate
- Goethe University Frankfurt, Edinger Institute (Neurological Institute), Frankfurt, Germany
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Hiroko Ohgaki
- International Agency for Research on Cancer, Lyon, France
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Bernhard Radlwimmer
- Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany
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Martin Zörnig
- Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus, Frankfurt, Germany
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Michel Mittelbronn
- Goethe University Frankfurt, Edinger Institute (Neurological Institute), Frankfurt, Germany
| Published: | September 11, 2012 |
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Outline
Text
The Far Upstream Element [FUSE] Binding Protein 1 (FUBP1) regulates target genes, such as the cell cycle regulators MYC and p21. FUBP1 is upregulated in many solid tumors and functions as an oncoprotein by stimulating proliferation and inhibiting apoptosis. Recently, FUBP1 mutations have been identified in approximately 15% of oligodendroglial tumors. To date, all reported FUBP1 mutations have been predicted to inactivate FUBP1, which suggests that FUBP1 functions as a tumor suppressor. As no data is currently available concerning FUBP1 protein expression levels in gliomas, we examined the FUBP1 expression profiles of human glial tumors by both immunohistochemistry and immunofluorescence. We subsequently analyzed FUBP1 expression related to the corresponding mutation status and expression profile of additional diagnostic markers. Our findings demonstrate that FUBP1 expression levels are significantly increased in all glioma subtypes as compared to normal central nervous system (CNS) control tissue. FUBP1 expression is associated with both proliferation and p53 accumulation, the latter independent from the TP53 mutation status. In addition, FUBP1 expression levels were significantly lower in cases with loss-of-heterozygosity (LOH) at the 1p locus. Furthermore, exon sequencing revealed a novel FUBP1 truncation mutation that was associated with loss of FUBP1 protein expression restricted to glioma cells. In summary, our findings indicate an association between FUBP1 expression and both proliferation and p53 accumulation in gliomas. Our findings further present FUBP1 immunohistochemical analysis as a potential supplementary additional diagnostic tool for neuropathological pre-screening for cases with a combined 1p LOH and FUBP1 mutation.
