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High Frequency of Temperature-Sensitive Mutants of p53 in Glioblastoma

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Pathology & Oncology Research

Abstract

Glioblastoma is the most common and the most aggressive type of brain cancer. Aberrations of the RTK/RAS/PI3K-, p53-, and RB cell signaling pathways were recognized as a core requirement for pathogenesis of glioblastoma. The p53 tumor suppressor functions as a transcription factor transactivating expression of its target genes in response to various stress stimuli. We determined the p53 status in 36 samples of glioblastoma by functional analyses FASAY and split assay. Seventeen p53 mutations were detected and further analyzed by cDNA and gDNA sequencing in 17 patients (47.2 %). Fifteen (88.2 %) of the mutations were missense mutations causing amino acid substitutions, seven of them exhibited temperature-sensitivity. Two mutations were determined as short deletions, one of them causing formation of premature termination codon in position 247. Fluorescent in situ hybridization revealed the loss of the p53-specific 17p13.3 locus in four of 33 analyzed samples (12 %). In 12 out of 30 samples (40 %), the p53 protein accumulation was shown by immunoblotting. There was high (80 %) concordance between the presence of the clonal p53 mutation and the p53 protein accumulation.

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Acknowledgement

We thank all the patients and their caregivers for participating in this study.

This work was supported by grants NT/13784-4 of the Internal Grant Agency of the Ministry of Health of the Czech Republic, MSM0021622434 of the Ministry of Education, Youth and Sports of the Czech Republic and by Regional Centre for Applied Molecular Oncology (RECAMO; CZ.1.05/2.1.00/03.0101) via the human resources project “IntegRECAMO: Intelectual Anchor” (CZ.1.07/2.3.00/20.0097).

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Authors and Affiliations

  1. Department of Pathology, University Hospital Brno, Jihlavska 20, 625 00, Brno, Czech Republic

    Jana Smardova, Kvetoslava Liskova, Miluse Svitakova & Leos Kren

  2. Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic

    Barbora Ravcukova

  3. Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic

    Lenka Kubiczkova & Sabina Sevcikova

  4. Advanced Cell Immunotherapy Unit, Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic

    Jaroslav Michalek

  5. Department of Neurosurgery, Faculty Hospital Brno, Brno, Czech Republic

    Vaclav Vybihal

  6. Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic

    Jan Smarda

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  1. Jana Smardova
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  2. Kvetoslava Liskova
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Correspondence to Jana Smardova.

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Smardova, J., Liskova, K., Ravcukova, B. et al. High Frequency of Temperature-Sensitive Mutants of p53 in Glioblastoma. Pathol. Oncol. Res. 19, 421–428 (2013). https://doi.org/10.1007/s12253-012-9596-7

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