Intergenic trans-splicing-driven formation of a chimeric FAM168B::ANKRD42 transcript in prostate cancer

Area of Science:

• Molecular Biology
• Cancer Genomics
• Bioinformatics

Background:

• Prostate cancer pathogenesis involves complex genetic and molecular alterations.
• Intergenic mRNA trans-splicing is an emerging mechanism in cancer biology.
• The roles of FAM168B and ANKRD42 in prostate cancer are not well understood.

Purpose of the Study:

• To identify and characterize novel chimeric transcripts in prostate cancer.
• To investigate the potential role of intergenic mRNA trans-splicing in prostate cancer development.
• To explore the functional implications of a newly discovered FAM168B::ANKRD42 fusion transcript.

Main Methods:

• DNA and RNA sequencing (RNA-seq) for transcript discovery.
• Analysis of chimeric split reads to confirm trans-splicing.
• Open reading frame (ORF) prediction for fusion peptide analysis.
• Integrative bio-computational analyses including kinase and transcription factor profiling.

Main Results:

• A novel intergenic mRNA trans-splicing event was identified, generating the FAM168B::ANKRD42 chimeric transcript.
• Chimeric split reads confirmed the trans-splicing origin, distinguishing it from genomic rearrangements.
• Bio-computational analyses implicated AKT1, AR, FOXA1, and E2F1 in the regulation of the fusion transcript.
• The FAM168B::ANKRD42 peptide is predicted to possess AKT1 phosphorylation sites, potentially modulating AR/FOXA1 signaling.

Conclusions:

• The study discovered a novel FAM168B::ANKRD42 chimeric transcript formed by intergenic mRNA trans-splicing in prostate cancer.
• This fusion transcript may play a role in cell cycle progression by influencing key signaling pathways.
• The chimeric FAM168B::ANKRD42 peptide is proposed as a potential driver of prostate cancer progression.