FHIT gene sequence variants and reduced fhit protein expression in glioblastoma multiforme
Date
2010-03
Authors
Güler, Gülnür
Aksoy, Kaya
Journal Title
Journal ISSN
Volume Title
Publisher
Springer/Plenum Publishers
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.
Description
Keywords
Glioblastoma multiforme, FHIT gene, Sequence alterations, SSCP, IHC, Common fragile sites, Cell lung-cancer, Tumor-suppressor gene, Brain-tumors, Breast-cancer, Turkish patients, Predisposition, Mutations, 3P14.2, Carcinoma, Cell biology, Neurosciences & neurology
Citation
Çeçener, G. vd. (2010). "FHIT gene sequence variants and reduced fhit protein expression in glioblastoma multiforme". Cellular and Molecular Neurobiology, 30(2), 301-307.