Fragile histidine triad (FHIT) gene, a candidate tumor suppressor gene located at 3p14.2, has been shown to be involved in carcinogenesis of many human tissues, including digestive tract tissues.
To establish an animal model and to explore the role of FHIT in tumorigenesis, we have developed a mouse strain carrying one or two inactivated Fhit alleles.
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.
The genetic susceptibility of codon 98 of the FHIT gene (3p14.2) in cervical carcinogenesis was determined by examining the effect of the gene and environmental factors vs. the different stages of cervical intraepithelial lesions and the different histopathologic types of invasive cervical cancers.
Our data indicate that LOH at chromosome 3p14.2-p25 is specific for conventional RCC and that loss of one allele of both the VHL and FHIT genes occurs in early stage of tumorigenesis.
The expression of the fragile histidine triad (FHIT) gene has been proposed to play an important role in early events of carcinogenesis and to be correlated with the progression or clinical outcomes of various cancers.
In addition, putative TSGs including FHIT, p16(INK4a), and p19(ARF) were selected for mutation screening to investigate their potential participation in NPC 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.
We conclude that the abnormalities of FHIT, presumably associated with the unstable nature of FRA3B within the FHIT gene, are involved in the carcinogenesis of gastric cancer, and lack of mismatch repair (MMR) could possibly promote its alteration in a subset of gastric tumours.
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.
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.
We conclude that 3p LOH is a universal phenomenon in RCC, but has different underlying mechanisms, molecular targets, and implications in the different morphotypes, although FHIT inactivation may play a role in both cRCC and chRCC tumorigenesis.
To determine alterations of fragile histidine triad (FHIT) gene in nasopharyngeal carcinoma and the correlation of FHIT gene with nasopharyngeal carcinogenesis.
We analyzed Fhit expression using an immunohistochemical method in invasive carcinoma, carcinoma in situ (CIS) and dysplasia, in paraffin sections of 75 esophageal squamous cell carcinomas (ESCs) to further elucidate the role of Fhit protein in esophageal carcinogenesis.
The complete loss of Fhit expression only in areas of neoplastic low differentiation suggests that FHIT gene takes part in late gastric carcinogenesis.
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.