FHIT Gene mutations and single nucleotide polymorphism in Indian oral and cervical squamous cell carcinomas

Abstract

Genetic alterations at the FHIT (fragile histidine triad) tumor suppressor gene have been found in various human cancers. We have made an attempt to find point mutations of this gene in two different cancers from India, with entirely different etiologic factors: oral cancer (55 samples) caused by chewing tobacco and cervical cancer (43 samples) caused mainly by HPV (human papilloma virus) infection. Analysis of tumor DNA by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method was performed on each of FHIT exons 5-9 individually, using exon-flanking primers. Two different mutations were identified in both oral and cervical tumors: one at the second nucleotide 3' to the termination codon (TGA) in exon 9 and the other at the ninth nucleotide upstream to the beginning of exon 9. These results indicate that mutations in the FHIT gene are rare events in these tumors in India (approximately 4%). In addition, we found a single nucleotide FHIT gene polymorphism which is due to T/A replacement at 17 nucleotides upstream to exon 9 where the A allele is 0.6 of the population.