Multiple molecular alterations of FHIT in betel‐associated oral carcinoma

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Abstract
To determine the alterations of the FHIT (fragile histidine triad) gene in oral squamous cell carcinoma (OSCC), this study examined mutation, promoter methylation, mRNA transcription, and protein expression of FHIT in OSCC associated mostly with the use of betel and/or tobacco. Analyses of the coding exons (exons 5–9) identified a deletion of one base in intron 4 in one tumour and a deletion of exon 7 in two tumours. Using bisulphite genomic sequencing, 28% of theinformative subjects exhibited promoter methylation. An aberrant FHIT transcript spanning from exon 3 to exon 10, which was verified by RT‐PCR analysis, was identified in 36% of the OSCC subjects, 50% of the oral pre‐invasive lesions, and 5% of the non‐cancerous match tissue.An abnormal immunohistochemical level of Fhit was detected in 41% of OSCC subjects. Astatistically significant association was found between aberrant transcription of the FHIT geneand an abnormal level of Fhit immunoreactivity. The results indicated that alteration ofFHIT is a frequent occurrence in OSCC and thus suggests that the aberrance in FHIT transcription could be an early event of oral carcinogenesis. Copyright © 2002 John Wiley & Sons, Ltd.