Abstract
OBJECTIVEFragile histidine triad (FHIT) gene located at chromosome 3p14.2 is a putative tumor suppressor gene involved in the pathogenesis of breast cancer. Both genetic and epigenetic alterations in FHIT have been implicated in breast carcinoma. In the present study, our main aim was to study the impact of these two kinds of alterations of FHIT gene in breast cancer patients of Kashmir.METHODSWe screened a total of 130 breast cancer patients of Kashmir by PCR-SSCP followed by direct sequencing and methylation specific PCR.RESULTSMutational screening of FHIT gene revealed significant amount of mutations [40.7% (53/130)] in five hot spot exons (exon 5-9), FHIT promoter was found to be hypermethylated in 59 of 130 [45.3%] breast cancer patients in our population.CONCLUSIONIn the present study we have shown a significant association between the mutational and hypermethylation profile of FHIT gene. Hence, we provide the first evidence to our knowledge that the significant association of FHIT mutation and hypermethylation leads to the complete inactivation of FHIT gene in patients with breast cancer. Silencing of the FHIT gene by promoter hypermethylation occurs in breast carcinomas, especially those with the significant amount of mutations.