Novel potential causative genes in carotid paragangliomas

Area of Science:

• Oncology
• Genetics
• Neuroscience

Background:

• Carotid paragangliomas (CPGLs) are rare neuroendocrine tumors originating at the carotid artery bifurcation.
• CPGLs account for a significant portion of head and neck paragangliomas and can be sporadic or hereditary.
• The genetic underpinnings and molecular pathogenesis of CPGLs are not fully understood, despite associations with approximately 30 genes.

Purpose of the Study:

• To identify novel causative genes in carotid paragangliomas.
• To elucidate the molecular mechanisms underlying CPGL development.
• To investigate the influence of genetic variants on gene expression in CPGLs.

Main Methods:

• High-throughput whole exome and transcriptome sequencing of CPGLs using Illumina platforms.
• Analysis of sequencing data with xseq to identify genes with mutations influencing expression (cis-effect).
• Utilized Nextera Rapid Capture Exome Kit and TruSeq Stranded Total RNA Library Prep Kit.

Main Results:

• Identified 16 candidate genes with variants potentially affecting gene expression.
• Observed the strongest cis-effect of loss-of-function variants in MYH15, CSP1, and MYH3.
• Predicted several likely pathogenic variants in these genes associated with CPGLs.

Conclusions:

• Three novel potential causative genes, MYH15, CSP1, and MYH3, were identified in carotid paragangliomas.
• These findings contribute to a better understanding of CPGL pathogenesis.
• The study highlights the utility of integrated exome and transcriptome sequencing for identifying novel cancer-related genes.