Summary To study abnormalities of the FHIT gene in human hepatocellular carcinoma (HCC), eight liver cancer cell lines, 18 matched tumorous and non-tumorous tissues from patients with HCC and three normal liver tissues were analysed by microsatellite polymorphism analysis and reverse transcription of FHITmRNA followed by polymerase chain reaction (PCR) amplification and sequencing of the products.No loss of heterozygosity at chromosome 3p14.2 as defined by markers D3S1300 and D3S1312 was detected in any of the specimens. In addition, a normal transcript of the gene without any sequence change was found to be expressed in all the cell lines, 17 of the 18 tumorous and all 21 non-tumorous liver tissues tested. Although five out of eight liver cancer cell lines (62.5%), 12 out of 18 HCC tissues (66.7%) and 8 out of 18 paired non-tumorous liver tissues (44.4%) displayed abnormal faint bands of smaller size, sequence analysis revealed that they were aberrant FH/Ttranscripts lacking three or more exons and might represent alternatively spliced transcripts only. In conclusion, these studies indicate that abnormalities of the FHIT gene transcripts occur in a fairly high frequency of tumorous and non-tumorous liver tissues.However, it might not be causally related to the hepatocarcinogenesis. Keywords: FHIT; HCC; RT-PCRHepatocellular carcinoma (HCC) is one of the most common human malignancies in the world, especially in areas such as China and sub-Saharan Africa (Okuda, 1992;Wright et al, 1992). It usually carries a grave prognosis. The precise aetiology of HCC is not yet clear, however it is well known that HCC is frequently associated with a background of chronic liver disease (Beasley et al, 1981). Predisposing factors include hepatitis B virus or hepatitis C virus infection and aflatoxin BI exposure (Okuda, 1992;Wright et al, 1992;Chen, 1993). Hepatocarcinogenesis is therefore considered as a multifactorial and multistep process that includes the activation of oncogenes and the inactivation of tumour-suppressor genes (Ding and Habib, 1994;Sugimura, 1992).Recently, the FHIT gene (fragile histidine triad gene), a candidate tumour-suppressor gene, was identified at 3pl4.2 . The gene spans the t(3;8) translocation breakpoint of familial renal cell carcinoma and contains the FRA3B fragile site (Cohen et al, 1979;Paradee et al, 1995;Ohta et al, 1996). It is the target of homozygous deletions in various human cancer cell lines, such as colon and gastric cancer cell lines . In addition, aberrant transcripts of the FHIT gene have been identified in 50% of primary gastrointestinal tumours , 80% of small-cell lung cancers and at least 40% of non-small-cell lung cancers (Sozzi et al, 1996a).In the current study, we examined 18 cases of HCCs and eight liver cancer cell lines for the presence of FHIT abnormalities. Microsatellite polymorphism analysis using primers at chromosome 3pl4 and reverse transcription (RT) of FHIT mRNA followed by the polymerase chain reaction (PCR) and sequencing of the products were performed.Received 2...