Our findings suggest essential roles of genes on these 3p loci, particularly the FHIT gene in participating in clonal selection and early development of cervical cancer.
In this study we investigated FHIT (Fragile Histidine Triad) protein alterations in cervical carcinomas to assess the relation of this gene with cervical cancer.
The finding of a statistically significant relationship between FHIT gene LOH and oncogenic HPV infection suggests a link between the integration of viral DNA and subsequent gene deletion in the progression of cervical cancer.
We analysed the expression of the fragile histidine triad (FHIT) gene in cervical cancer to evaluate its clinical relevance in relation to human papillomavirus (HPV) infection.
Our findings suggest an association between HPV infection and FHIT gene abnormalities raising the possibility of a mechanistic role for the FHIT gene as a cofactor with HPV in triggering the development of cervical cancer.
There was more FHIT promoter methylation in cervical cancer than in cervical intraepithelial neoplasia lesions and normal controls (odds ratio = 8.0, p = 0.055; odds ratio = 10.75, p < 0.001, respectively).
These findings demonstrate that truncated FHIT transcripts are commonly detected in both normal and tumor tissues, and suggest that these altered transcripts are not causally related to tumorigenesis in cervical cancer.
The candidate tumor suppressor gene FHIT has been mapped to 3p14.2, and previous studies have demonstrated reduced or aberrant FHIT transcripts and reduced or absent Fhit protein expression in a large percentage of cervical cancer-derived cell lines and primary cervical carcinomas.
FRA3B is the most frequently expressed common fragile site localized within human chromosomal band 3p14.2, which is frequently deleted in many different cancers, including cervical cancer.
Thus, WWOX may be considered as a novel important genetic marker in cervical cancer and the association between the altered expression of FHIT and WWOX may be a critical event in the progression of this neoplasia.