Aberrant splicing of FHIT transcripts in human gastric cancer cell lines

Alterations of the FHIT gene occur as frequent events in several human cancers. Replacement of exogenous wild-type FHIT gene has been shown to induce suppression of tumorigenicity of human FHIT-negative cells in nude mice and aberrant FHIT transcripts have been observed in a variety of human solid tumors. In the presence study, we performed a nested reverse transcription-polymerase chain reaction (RT-PCR) analysis to identify aberrant FHIT transcripts in 6 gastric cancer cell lines. In addition to the wild-type FHIT transcript, small-sized transcripts with various number and lengths were observed in all of the cell lines examined. Sequence analysis confirmed that different types of truncated transcripts included exonic deletions, insertions of intron 5 sequences between exons, and combinations of both. Most of these transcripts lacked exon 5 in which translation initiation codon is located. Aberrant transcripts with partial exonic deletions, resulting from activation of cryptic splice sites, were also observed in 5 cell lines. Additionally, multi-step splice patterns, indicative of additional downstream processing, were observed in several cancer lines. Our results suggest that the aberrant FHIT transcripts in gastric cancer cell lines resulted from faulty splicing, including exon skipping, selection of cryptic splice site and additional downstream splice processing.