Comprehensive exploration of novel chimeric transcripts in clear cell renal cell carcinomas using whole transcriptome...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Clear cell renal cell carcinoma (RCC) is a significant health concern.
• The role of chimeric transcripts in renal carcinogenesis remains unclear.
• Understanding genetic alterations in RCC is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the involvement of chimeric transcript expression in renal carcinogenesis.
• To identify novel chimeric transcripts in clear cell RCC.
• To assess the impact of chimeric transcripts on gene expression and patient outcomes.

Main Methods:

• Whole transcriptome analysis (RNA sequencing) and deFuse program for chimeric transcript identification.
• Reverse transcription (RT)-PCR and Sanger sequencing for verification.
• Quantitative RT-PCR to analyze mRNA expression levels of partner genes.

Main Results:

• 26 novel chimeric transcripts identified in 25% of clear cell RCC cases.
• Genomic breakpoints determined for five chimeric transcripts.
• Significantly reduced mRNA expression of partner genes (e.g., MMACHC, PTER, EPC2) in tumor tissues compared to normal tissues.
• Reduced expression of partner genes correlated with tumor aggressiveness and poorer patient outcomes.

Conclusions:

• Chimeric transcript generation may contribute to renal carcinogenesis.
• Reduced expression of partner genes, potentially due to involvement in chimeric transcripts, may drive malignant progression.
• Chimeric transcripts can induce dysfunction in tumor-related genes, impacting RCC development.