Abnormalities of the FHIT gene in human oral carcinogenesis

The abnormalities of the fragile histidine triad (FHIT) gene in tissue samples of oral squamous cell carcinomas (SCCs) along with several leukoplakias and an erythroplakia were examined to determine whether the FHIT gene is actually a frequent target in vivo for alteration during oral carcinogenesis. Abnormal transcripts of the FHIT gene were found in eight of 15 oral SCCs. Although these abnormal transcripts varied widely, deletion patterns incorporating a deletion of exon 5 were the most common. Loss of heterozygosity (LOH) analysis demonstrated that the abnormal FHIT transcripts found in cancer cells were attributable to abnormalities of the FHIT gene. Abnormal FHIT transcripts were also observed in two of seven premalignant lesions. Interestingly, in the case of one patient with a premalignant lesion showing an abnormal FHIT transcript, subsequent oral SCC developed during a 3-year follow-up period. On the other hand, in the two patients from whom both leukoplakia and SCC samples were taken simultaneously, abnormal FHIT transcripts were found only in the SCCs. Although the functional role of FHIT remains to be clarified, these results suggest that the FHIT alteration is actually involved in carcinogenesis of the oral epithelium.