Exp Mol Med.  2001 Sep;33(3):124-130.

Characterization of aberrant FHIT transcripts in gastric adenocarcinomas

• Lee SH
• Kim CJ
• Park HK
• Koh JW
• Cho MH
• Baek MJ
• Lee MS

Abstract

Aberrant transcripts of FHIT (fragile histidine triad) have been reported in several types of primary tumors and cell lines, including gastric carcinoma. The role of these aberrant transcripts in tumorigenesis is not clear yet. Forty-eight aberrant-sized FHIT transcripts with various lengths and number in 35 cases of gastric adenocarcinomas were further characterized. Aberrant transcripts, with deletions and/or insertions, were frequently observed in 20 cases of tumors. Sequence analysis demonstrated that different types of aberrant transcripts used normal splice sites but skipped exons, contained the inserts with the part of intron 5 sequences, or used the FHIT cDNA sequence 179-180 as a cryptic splice acceptor site. Most of aberrant transcripts lacked exon 5 and were presumably non-functional as the translation initiation codon is located in exon 5. Additionally, other transcripts, indicative of additional splice processing, either deletions or insertions, were expressed in several tumors. Taken together, our data indicate that the FHIT gene expression is frequently altered in gastric adenocarcinomas by aberrant splicing, and suggest that different types of aberrant transcripts may result during the multi-step splice processing.

Keyword

FHIT; gastric adenocarcinoma; aberrant transcript; carcinogenesis; splicing fidelity

MeSH Terms

Adenocarcinoma/*genetics/metabolism
Base Sequence
Exons
Genes, Tumor Suppressor
Human
Molecular Sequence Data
Neoplasm Proteins/*genetics/metabolism
RNA Splicing/*genetics
RNA, Messenger/genetics/metabolism
RNA, Neoplasm/genetics/metabolism
Reverse Transcriptase Polymerase Chain Reaction
Stomach Neoplasms/*genetics/metabolism
Support, Non-U.S. Gov't
Transcription, Genetic