Mutational load in carotid body tumor

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Carotid body tumors (CBTs) are rare neoplasms originating from paraganglia near the carotid artery bifurcation.
• CBTs display significant intra-tumor heterogeneity, with potential links to germline and somatic genetic variants.
• Limited studies exist on CBT molecular genetics, leaving pathogenesis mechanisms incompletely understood.

Purpose of the Study:

• To estimate the mutational load (ML) in carotid body tumors (CBTs).
• To explore the molecular genetic landscape of CBTs.
• To contribute to understanding CBT pathogenesis and tumor biology.

Main Methods:

• Exome sequencing was performed on tumor tissues, matched lymph nodes, and peripheral blood from six CBT patients using the NextSeq 500 platform.
• A specialized data analysis approach was developed and applied to ensure reliable results, particularly for tumors with low ML.
• Mutational load was quantified as somatic variants per megabase (Mb) within targeted regions using the Illumina TruSeq Exome Library Prep Kit.

Main Results:

• The estimated ML in CBTs ranged from 0.09 to 0.28 per Mb.
• Several pathogenic/likely pathogenic somatic and germline allelic variants were identified across the six patients, including variants in the TP53 gene.
• The identified variants involved known paraganglioma/pheochromocytoma-causative genes and potentially novel genes.

Conclusions:

• The developed methodology allowed for accurate ML estimation in CBTs, revealing a significantly lower load compared to common malignant tumors.
• Identified genetic variants may play a role in the pathogenesis of CBTs.
• This study enhances the understanding of the mutation process and tumor development biology in carotid body tumors.