Altered splicing pattern of TACC1 mRNA in gastric cancer.

Transforming acidic coiled-coil (TACC) proteins are centrosome and microtubule-associated proteins that are essential for mitotic spindle function. We identified TACC1 as an immunogenic protein and a potential tumor antigen by applying serological identification of antigens by recombinant expression cloning (SEREX) technique to screen a gastric cancer cDNA library. The 5'RLM-RACE and reverse transcriptase polymerase chain reaction analyses revealed at least six different transcript variants of TACC1 with variable transcription start sites and alternative exon usage (designated TACC1-A-TACC1-F). All transcripts differ in their 5' ends but share an identical 3' region encoding coiled-coil domain. Four transcripts were universally expressed in all normal tissues analyzed but TACC1-D and TACC1-F showed a restricted expression pattern. TACC1-F, a transcript representing the SEREX-identified cDNA clone, was predominantly expressed in brain and gastric tumors to a similar level. TACC1-D was only weakly detectable in kidney and colon but not in other normal tissues, while a relatively strong expression was observed in 50% of gastric cancer tissue samples analyzed. These transcript variants are generated possibly as a result of alterations in efficiency and pattern of alternative splicing; these isoforms may represent genetic markers, for example TACC1-D for gastric cancer. We also propose that inappropriate expression of the isoforms in gastric cancer cells might result in dysfunction of TACC1 thus contributing to the genetic instability.