Splice-disrupt genomic variants in prostate cancer

Area of Science:

• Genomics
• Cancer Biology
• Molecular Genetics

Background:

• Splice-disrupting genomic variants contribute to cancer-causing errors in gene expression.
• Knowledge regarding splice-disrupting genomic variants remains limited.

Purpose of the Study:

• To investigate the patterns and target genes of splice-disrupting variants in various prostate cancer types.
• To identify high-risk splice-disrupting variants and their functional implications in prostate cancer.

Main Methods:

• Analysis of 21,842,764 genomic variants across different prostate cancer subtypes.
• Identification of splice-disrupting variants in key genes like HLA-A, MSR1, and EGFR.
• Utilized computational tools (PolyPhen, SIFT, GERP++) and dbSNP for variant risk assessment.

Main Results:

• Identified specific splice-disrupting variants in HLA-A, MSR1, and EGFR with high allele frequencies.
• Discovered splice-disrupting variants in NCOR2, PTPRC, and CRP exclusively in advanced metastatic castration-resistant prostate cancer.
• Functional annotation linked damaging variants to endocrine resistance, metabolic processes, and cell cycle regulation.

Conclusions:

• This is the first comprehensive profiling of splice-disrupting genomic variants and their target genes in prostate cancer.
• Unraveling alternative splicing mechanisms presents opportunities for novel diagnostic and prognostic markers.
• Highlights the importance of variants like rs1800716 in CYP2D6 for RNA splicing and drug interactions.