Our findings support the conclusion that FHIT/FRA3B abnormalities are associated with lung cancer pathogenesis but that FHIT abnormalities differ from the types of mutations and lack of wild-type transcript found in classic tumor suppressor genes, and functional studies are needed to define the role of FHIT in thoracic tumorigenesis.
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.
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.
However, taken together, our results provide evidence that breakage and rearrangement within the FRA3B fragile site sequences result in alterations of FHIT and are likely to be involved in carcinogenesis.
To evaluate the significance of FHIT gene abnormalities in gastric carcinogenesis, we examined the allelic status and transcripts of the gene in 23 primary gastric carcinomas as well as 7 gastric carcinoma cell lines.
The frequent alterations in FHIT expression in many cervical carcinomas, but not in normal tissues, suggest that FHIT gene alterations may play an important role in cervical tumorigenesis.
In addition, absence of Fhit protein in some precancerous dysplastic lesions suggested that FHIT inactivation may occur at an early phase of lung carcinogenesis.
Abnormalities of the FHIT gene were found in many carcinoma cell lines and human tumors as reported which suggest an etiological function in 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.
While RARbeta is presently included in Region II, the minimal regions of deletion exclude VHL, TGFBR2, PTPase(gamma) and FHIT as candidate tumor suppressors in ovarian tumorigenesis.
Because the same reverse transcription-polymerase chain reaction expression pattern was observed in both normal and tumor-derived primary cell cultures, these results argue against a significant role for FHIT in epithelial ovarian tumorigenesis.
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.
To investigate whether FHIT inactivation plays a role in early lung tumorigenesis, Fhit levels were determined by immunohistochemistry in tumors from 87 patients with stage I NSCLC and in 372 bronchial biopsy specimens from 86 chronic smokers without evidence of malignancy.
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 fragile histidine triad (FHIT) gene at chromosome region 3p14.2 is a candidate tumor suppressor gene that may play a role in cervical tumorigenesis.
Consequently, the paucity of documented inactivating point mutations cannot be used to judge the presence or absence of putative FHIT-related selective pressures that act during tumorigenesis of RER(-) neoplasia.