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FHIT Gene Sequence Variants and Reduced Fhit Protein Expression in Glioblastoma Multiforme

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Abstract

Molecular studies have an important role in the elucidation of the mechanisms involved in Glioblastoma multiforme (GBM) development. The occurrence of FHIT gene alterations, which has an important role in different cancers, has not yet been studied well in GBM. We aimed to investigate the occurrence of alterations of FHIT gene sequence and protein expression in the GBMs. Sequence alterations in exons 5–9 of the FHIT gene were screened in 63 GBMs using the single-strand conformational polymorphism method, followed by DNA sequencing. Additionally, the level of Fhit protein expression in tissues of 48 tumors was assessed by immunohistochemistry (IHC). In our investigation, FHIT gene alterations in the coding region were detected in 11 of the 63 GBM cases (17.5%). Two different sequence variants were determined: one novel missense variant (G→C transition at codon 49) and one previously described silent alteration (C→T transition at codon 88). Using web-based programs, such as SIFT and ESEfinder, it was determined that both alterations might have caused significant modification on protein function. In addition, we identified a previously reported an intronic polymorphism (T→A transition at IVS8-17) in 47.5% of cases as a similar rate (45%) in the control group. Moreover, it was observed that Fhit protein expression was reduced in 87.5% of tumors. In conclusion, the reduction or loss of Fhit protein expression by genetic alterations or epigenetic mechanisms in GBM might be associated with brain tumorigenesis.

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Abbreviations

GBM:

Glioblastoma multiforme

IHC:

Immunohistochemistry

PCR:

Polymerase chain reaction

SSCP:

Single strand conformational polymorphism

WHO:

World Health Organization

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Acknowledgments

We would like to thank Professor Dr. Kay Huebner in the Comprehensive Cancer Center, Ohio State University for her suggestions and kindly providing Fhit antiserum. We thank Dr. Ediz in the Biostatistics Department, Medical Faculty of Uludag University for his expert advice. We also thank Prizma and Elips Ltd for their support in dealing with experimental equipment.

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Authors and Affiliations

  1. Department of Medical Biology, School of Medicine, Uludag University, Bursa, Turkey

    Gulsah Cecener, Berrin Tunca & Unal Egeli

  2. Department of Neurosurgery, School of Medicine, Uludag University, Bursa, Turkey

    Ahmet Bekar

  3. Department of Pathology, School of Medicine, Hacettepe University, Ankara, Turkey

    Gulnur Guler

  4. Department of Pathology, School of Medicine, Uludag University, Bursa, Turkey

    Sahsine Tolunay

  5. Department of Neurosurgery, Acıbadem Hospital, Bursa, Turkey

    Kaya Aksoy

Authors
  1. Gulsah Cecener
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  2. Berrin Tunca
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  3. Unal Egeli
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  4. Ahmet Bekar
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  5. Gulnur Guler
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  6. Sahsine Tolunay
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  7. Kaya Aksoy
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Correspondence to Gulsah Cecener.

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Cecener, G., Tunca, B., Egeli, U. et al. FHIT Gene Sequence Variants and Reduced Fhit Protein Expression in Glioblastoma Multiforme. Cell Mol Neurobiol 30, 301–307 (2010). https://doi.org/10.1007/s10571-009-9452-9

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  • DOI: https://doi.org/10.1007/s10571-009-9452-9

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