Novel RNA variants in colorectal cancers

Area of Science:

• Genomics
• Molecular Biology
• Oncology

Background:

• Colorectal cancer (CRC) presents a significant global health challenge with high incidence and moderate survival rates.
• Identifying novel RNA variants is crucial for understanding CRC pathogenesis and discovering new diagnostic or therapeutic targets.

Purpose of the Study:

• To identify and characterize novel RNA variants, including fusion events and alternative transcript structures, specific to colorectal cancer.
• To develop and apply a high-throughput sequencing method for efficient discovery of these RNA variants.

Main Methods:

• Analysis of exon-level microarray expression data from 202 colorectal cancer samples.
• Development and application of rapid amplification of cDNA ends followed by high-throughput sequencing (RACE-seq) for transcript structure investigation.
• Validation of identified variants using external RNA-sequencing datasets.

Main Results:

• Nominated 25 genes with altered 3' expression in CRC samples.
• Identified three private fusion events (VWA2-TCF7L2, DHX35-BPIFA2, CASZ1-MASP2) and novel transcript structures in 17 other candidate genes.
• Discovered a recurrent read-through fusion transcript (KLK8-KLK7) and a splice variant (S100A2) overrepresented in CRC tissues and cell lines.

Conclusions:

• The high-throughput RACE-seq approach effectively identified colorectal cancer-specific RNA variants.
• The discovered RNA variants, including fusion transcripts and splice variants, represent potential novel biomarkers for CRC.