Non-Susceptibility Gene Variants in Head and Neck Paragangliomas

Snezhkina, Anastasiya V.; Pavlov, Vladislav S.; Krasnov, George S.; Kalinin, Dmitry V.; Pudova, Elena A.; Stolbovskaya, Olga V.; Dunshina, Anastasiya V.; Fedorova, Maria S.; Kudryavtseva, Anna V.

doi:10.3390/ijms252312762

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Open AccessArticle

Non-Susceptibility Gene Variants in Head and Neck Paragangliomas

by

Anastasiya V. Snezhkina

^1,*

,

Vladislav S. Pavlov

¹

,

George S. Krasnov

¹

,

Dmitry V. Kalinin

²,

Elena A. Pudova

¹

,

Olga V. Stolbovskaya

³,

Anastasiya V. Dunshina

⁴,

Maria S. Fedorova

¹

and

Anna V. Kudryavtseva

¹

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia

²

Vishnevsky Institute of Surgery, Ministry of Health of the Russian Federation, 117997 Moscow, Russia

³

Department of Human Anatomy, Ulyanovsk State University, 432017 Ulyanovsk, Russia

⁴

Ulyanovsk Regional Clinical Oncological Dispensary, 432068 Ulyanovsk, Russia

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2024, 25(23), 12762; https://doi.org/10.3390/ijms252312762 (registering DOI)

Submission received: 12 November 2024 / Revised: 21 November 2024 / Accepted: 22 November 2024 / Published: 27 November 2024

(This article belongs to the Special Issue Genetic Mutations in Health and Disease)

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Abstract

Head and neck paragangliomas (HNPGLs) are rare neoplasms that, along with pheochromocytomas and extra-adrenal paragangliomas, are associated with inherited mutations in at least 12 susceptibility genes in approximately 40% of cases. However, due to the rarity of HNPGLs, only a series of small-scale studies and individual cases have reported mutations in additional genes that may be involved in tumorigenesis. Consequently, numerous disease-causing mutations and genes responsible for the pathogenesis of HNPGLs remain poorly investigated. The aim of this study was to gain a deeper understanding of the genetic basis of HNPGLs by focusing on variants in genes that were not previously identified as well-known drivers. A whole-exome data analysis was conducted on a representative set of 152 HNPGLs. In 30% of the tumors examined, 53 potentially deleterious variants were identified in 36 different genes. The analysis identified pathogenic or likely pathogenic variants in the ARNT, IDH2, L2HGDH, MYH3, PIK3CA, and TERT genes. A functional network analysis of the mutated genes revealed numerous associations and a list of metabolic pathways (e.g., the TCA cycle, carbon metabolism, pyruvate metabolism, etc.) and signaling pathways (e.g., HIF1, PI3K-Akt, FoxO, AMPK, MAPK, etc.) that may play an important role in the development of HNPGLs. The identified range of genetic alterations affecting multiple genes and, potentially, influencing diverse cellular pathways provides an enhanced molecular genetic characterization of HNPGLs.

Keywords: head and neck paragangliomas; genetic screening; mutations; gene network

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MDPI and ACS Style

Snezhkina, A.V.; Pavlov, V.S.; Krasnov, G.S.; Kalinin, D.V.; Pudova, E.A.; Stolbovskaya, O.V.; Dunshina, A.V.; Fedorova, M.S.; Kudryavtseva, A.V. Non-Susceptibility Gene Variants in Head and Neck Paragangliomas. Int. J. Mol. Sci. 2024, 25, 12762. https://doi.org/10.3390/ijms252312762

AMA Style

Snezhkina AV, Pavlov VS, Krasnov GS, Kalinin DV, Pudova EA, Stolbovskaya OV, Dunshina AV, Fedorova MS, Kudryavtseva AV. Non-Susceptibility Gene Variants in Head and Neck Paragangliomas. International Journal of Molecular Sciences. 2024; 25(23):12762. https://doi.org/10.3390/ijms252312762

Chicago/Turabian Style

Snezhkina, Anastasiya V., Vladislav S. Pavlov, George S. Krasnov, Dmitry V. Kalinin, Elena A. Pudova, Olga V. Stolbovskaya, Anastasiya V. Dunshina, Maria S. Fedorova, and Anna V. Kudryavtseva. 2024. "Non-Susceptibility Gene Variants in Head and Neck Paragangliomas" International Journal of Molecular Sciences 25, no. 23: 12762. https://doi.org/10.3390/ijms252312762

APA Style

Snezhkina, A. V., Pavlov, V. S., Krasnov, G. S., Kalinin, D. V., Pudova, E. A., Stolbovskaya, O. V., Dunshina, A. V., Fedorova, M. S., & Kudryavtseva, A. V. (2024). Non-Susceptibility Gene Variants in Head and Neck Paragangliomas. International Journal of Molecular Sciences, 25(23), 12762. https://doi.org/10.3390/ijms252312762

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Non-Susceptibility Gene Variants in Head and Neck Paragangliomas

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