In addition, putative TSGs including FHIT, p16(INK4a), and p19(ARF) were selected for mutation screening to investigate their potential participation in NPC tumorigenesis.
As alterations of chromosome 3p are common events in ovarian cancers with breakpoint sites at 3p14.2, we decided to investigate the role of FHIT in human ovarian tumorigenesis.
To clarify further the role of the Fhit protein in gastric carcinogenesis, we investigated whether Fhit expression in early gastric neoplasia is associated with mismatch repair protein expression and cellular phenotype.
Methylation of the FHIT gene is associated with transcriptional inactivation in esophageal squamous cell carcinoma, and FHIT inactivation has been linked to smoking-related carcinogenesis.
These results suggest that members of the HIT family of genes are only selectively involved in tumorigenesis and that perturbation of FHIT gene expression is an early event in colorectal tumorigenesis.
The coincidence of a chromosomal fragile site, FRA3B, at a common chromosomal breakpoint in lung cancer has suggested that fragility at this site may predispose to breakage that could contribute to multistep carcinogenesis.
To investigate the potential role of FHIT in thyroid tumorigenesis, we examined 57 thyroid tumour specimens (eight benign adenomas, 40 papillary, four follicular and five anaplastic carcinomas), and two thyroid carcinoma cell lines (NPA, SW579) for genetic alterations by using reverse transcription-polymerase chain reaction (RT-PCR), PCR product sequencing, single-strand conformation polymorphism (SSCP) and Southern blot analysis.
In addition, absence of Fhit protein in some precancerous dysplastic lesions suggested that FHIT inactivation may occur at an early phase of lung carcinogenesis.
These results indicate that p16 and FHIT methylation may be one of the earliest events and an important mechanism for gene silencing in esophageal squamous cell carcinogenesis.
Northern analyses with the exon 2a of the familial and the metastatic RCC demonstrates concurrent loss of expression of a 4.4 kb transcript with the loss of the E2a sequence, suggesting that exon 2a of the FHIT gene may play an important role in the oncogenesis of renal cell carcinoma.
Our data indicate that allelic loss of the FHIT gene is neither a critical event in carcinogenesis of primary brain tumors nor tumor grade-associated in astrocytic tumors.
Thus, genetic alterations within the FHIT gene, leading to loss of Fhit protein, may play an important role in the carcinogenesis of a significant number of sporadic lobular breast cancers, even though the apparent frequency of genomic alterations within the gene is lower than in ductal breast cancer.
This literature review aims to clarify the involvement of the FHIT gene in carcinogenesis, tumor progression and clinical outcome in prevalent solid malignancies, such as breast, lung, cervical, esophageal, gastric and colorectal cancers.
The fragile histidine triad (FHIT) gene at chromosome region 3p14.2 is a candidate tumor suppressor gene that may play a role in cervical tumorigenesis.
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 results of LOH, real-time qRT-PCR and imunohistochemical analyses were correlated with clinico-pathological characteristics of patients and their tumors in order to evaluate the role of FHIT gene/protein in sporadic colon adenocarcinoma tumorigenesis.
FHIT hypermethylation, which induces the inactivation of FHIT gene, plays an important role in the carcinogenesis and clinical outcome and may serve as a potential drug target of NSCLC.
Nevertheless, high frequency of aberrant FHIT transcripts, significant rate of LOH at D3S1300, and altered expression of the FHIT protein indicate that alterations of the FHIT gene can play an important role in gastric carcinogenesis.