Integrated transcriptomic profiling reveals oncogenic pathways and chimeric transcripts in equine sarcoid lesions...

Area of Science:

• Veterinary Oncology
• Equine Dermatology
• Molecular Biology

Background:

• Equine sarcoids are the most common skin tumors in horses, often caused by Bovine Papillomavirus (BPV).
• These tumors are known for their therapeutic resistance and high recurrence rates, posing a significant challenge in equine health management.
• Understanding the molecular basis of sarcoid development is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the molecular pathogenetic mechanisms of equine sarcoids using a transcriptomic approach.
• To identify differentially expressed genes (DEGs) and microRNAs (miRNAs) in sarcoid tissues compared to healthy skin.
• To explore the potential role of chimeric transcripts in the oncogenesis of equine sarcoids.

Main Methods:

• High-throughput Illumina sequencing was used to analyze mRNA and small RNA expression in 12 equine sarcoids and 12 healthy skin samples.
• Samples were tested for viral DNA, and differentially expressed genes and miRNAs were identified.
• Computational analysis was employed to detect chimeric transcripts associated with viral integration events.

Main Results:

• Over 6,000 DEGs and 145 differentially expressed miRNAs were identified, indicating significant transcriptional differences between sarcoids and healthy skin.
• Enriched biological processes included growth factors, collagen binding, cell migration, proliferation, and inflammation.
• Six fusion loci, including a frequent WNT10B and FKBP11 fusion, were identified, representing the first report of chimeric transcripts in equine sarcoids.

Conclusions:

• Equine sarcoids exhibit substantial transcriptional dysregulation compared to healthy skin, with processes related to cellular transformation being significantly enriched.
• The identification of chimeric transcripts, particularly the WNT10B/FKBP11 fusion, provides novel insights into BPV-driven oncogenesis in horses.
• These findings open new avenues for understanding and potentially targeting the molecular pathways involved in equine sarcoid development.