Clinicopathologic features and FHIT gene expression in sporadic colorectaladenocarcinomas

Background: The putative tumour suppressor gene FHIT (fragile histidine tri ad) spans the common fragile site FRA3B, which is highly susceptible to bre aks and deletions induced by genotoxic agents. Tumours associated with expo sure to carcinogens, such as colorectal adenocarcinomas, should be particul arly susceptible to alterations in the FHIT gene. We studied the frequency of FHIT alterations and their correlations with clinicopathologic features in sporadic colon carcinomas. Methods: FHIT expression was investigated by reverse transcription polymerase chain reaction in 56 primary sporadic colo rectal carcinomas. The same rumours and matched normal tissues were also in vestigated for loss of heterozygosity by using two markers located inside t he FHIT gene. Results: Twenty-nine of 56 tumours (51.8%) expressed aberrant FHIT transcripts. Four tumours had absence or nearly undetectable levels o f the normal-sized FHIT transcript. Sequencing analysis of the altered tran scripts showed FHIT mRNA lacking one or more exons, more frequent deletions of exons 4-5-6 or 4-5-6-7-8. At the genomic level 46.4% (13 of 28) of the cases showed alterations involving FHIT locus. We did not find any correlat ion between FHIT gene alterations and clinicopathologic characteristics of the rumours. Conclusions: Since the FHIT gene is frequently altered, its ro le in the molecular pathogenesis of sporadic colon carcinoma deserves furth er investigation.