The gene is inactivated by deletions in cancer-derived cell lines and primary tumors and Fhit protein is absent or reduced in lung, stomach, kidney, and cervical carcinomas, consistent with function as a tumor suppressor.
To determine the role of the FHIT gene in cervical and uterine carcinomas, 16 cases of cervical carcinoma and 7 cases of endometrial carcinoma, as well as nearby non-cancerous tissues in these patients, were analyzed by reverse transcription of the FHIT mRNA followed by polymerase chain reaction amplification and sequencing of the products.
These results suggest that FHIT gene abnormalities are infrequent in primary gastric carcinomas and that the frequent homozygous deletions seen in cell lines might simply reflect the plasticity of the genome at FRA3B under culture conditions.
Immunohistochemical analysis of Fhit expression in cervical tissues revealed strong immunoreactivity in nonneoplastic squamous and glandular cervical epithelium and marked reduction or loss of Fhit protein in 25 of 33 (76%) primary cervical carcinomas.
The first information about FHIT, a candidate suppressor gene recently identified in the FRA3B fragile site in 3p14 and found to be abnormal or lost in a high percentage of carcinomas of various organs, including breast, is compatible with such a general proliferation-regulating role.