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.