Novel fusion transcripts in bladder cancer identified by RNA-seq.

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Urothelial carcinoma (UC) is the most common type of bladder cancer.
• Identifying novel fusion genes in UC could offer new insights into its classification and significance.

Purpose of the Study:

• To identify and characterize novel fusion transcripts in bladder cancer using high-throughput RNA sequencing.
• To investigate the prevalence and specificity of identified fusion genes in UC specimens.

Main Methods:

• High-throughput RNA sequencing was performed on three UC samples to identify fusion candidates.
• Stringent criteria were applied to nominate 10 candidate fusion transcripts.
• Four novel fusion genes (SEPT9/CYHR, IGF1R/TTC23, SYT8/TNNI2, CASZ1/DFFA) were validated in 48 formalin-fixed paraffin-embedded (FFPE) bladder cancer specimens.

Main Results:

• Four novel fusion genes were identified and validated.
• SEPT9/CYHR, IGF1R/TTC23, and CASZ1/DFFA fusions, resulting from chromosomal rearrangements, were rare or absent in the studied samples.
• The SYT8/TNNI2 fusion transcript, arising from read-through transcription, was found in 37.5% (18/48) of UC specimens and was tumor-specific.

Conclusions:

• The SYT8/TNNI2 fusion transcript is a common and tumor-specific event in urothelial carcinoma.
• Further research is needed to elucidate the functional and clinical relevance of these novel fusion genes in bladder carcinogenesis.