Mutation Frequency in Main Susceptibility Genes Among Patients With Head and Neck Paragangliomas.

Anastasiya V Snezhkina,Elena A Pudova,Galina S Alekseeva,Alexander L Golovyuk,Andrey A Poloznikov,Dmitry V Kalinin,Andrey D Kaprin,Zulfiya G Guvatova,George S Razmakhaev,Anna V Kudryavtseva,Maria S Fedorova,Vladislav S Pavlov,Alexey A Dmitriev,Nataliya V Melnikova,George S Krasnov

doi:10.3389/fgene.2020.614908

Abstract

Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors that have a high degree of heritability and are predominantly associated with mutations in ten genes, such as SDHx, SDHAF2, VHL, RET, NF1, TMEM127, MAX, FH, MEN2, and SLC25A11. Elucidating the mutation prevalence is crucial for the development of genetic testing. In this study, we identified pathogenic/likely pathogenic variants in the main susceptibility genes in 102 Russian patients with HNPGLs (82 carotid and 23 vagal paragangliomas) using whole exome sequencing. Pathogenic/likely pathogenic variants were detected in 43% (44/102) of patients. We identified the following variant distribution of the tested genes: SDHA (1%), SDHB (10%), SDHC (5%), SDHD (24.5%), and RET (5%). SDHD variants were observed in the majority of the patients with bilateral/multiple paragangliomas. Thus, among Russian patients with HNPGLs the most frequently mutated gene was SDHD followed by SDHB, SDHC, RET, and SDHA.

Highlights

Head and neck (HN) paragangliomas (PGLs) are rare neuroendocrine tumors of four distinct localizations: carotid, vagal, laryngeal, and middle ear PGLs
A representative set of Head and neck paragangliomas (HNPGLs) samples were collected from 102 Russian patients diagnosed with Carotid paragangliomas (CPGLs) (n = 82) and VPGLs (n = 23), including 76 patients with single CPGL, 20 patients with single VPGL, and 6 patients with bilateral/multiple PGLs (Table 1)
These tumor samples were analyzed for the presence of pathogenic/likely pathogenic variants in the main susceptibility genes for HNPGLs: SDHx, SDHAF2, VHL, RET, NF1, TMEM127, MAX, FH, multiple endocrine neoplasia type 2 (MEN2), and SLC25A11

Summary

Introduction

Head and neck (HN) paragangliomas (PGLs) are rare neuroendocrine tumors of four distinct localizations: carotid, vagal, laryngeal, and middle ear PGLs. Carotid paragangliomas (CPGLs) arise from the carotid glomus at the carotid artery bifurcation and are the most common form of HNPGLs (60%) (El-Naggar et al, 2017). Middle ear and vagal paragangliomas (MEPGLs and VPGLs) are less frequent than CPGLs and account for 29% and 13%, respectively; laryngeal PGLs are very rare (El-Naggar et al, 2017). All the HNPGLs are often characterized by slow growth and non-aggressive behavior, but exhibit metastatic potential. The overall metastatic rate for HNPGLs vary depending on the site of tumor localization: 2% for larynx and middle ear, 4–6% for carotid, and up to 16% for vagal PGLs (Williams, 2017). HNPGLs can develop as bilateral or multiple tumors and pose significant treatment challenges

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