Mutation profiling in eight cases of vagal paragangliomas
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RESEARCH
Open Access
Mutation profiling in eight cases of vagal paragangliomas Anna V. Kudryavtseva1*, Dmitry V. Kalinin2, Vladislav S. Pavlov1, Maria V. Savvateeva1, Maria S. Fedorova1, Elena A. Pudova1, Anastasiya A. Kobelyatskaya1, Alexander L. Golovyuk2, Zulfiya G. Guvatova1, George S. Razmakhaev3, Tatiana B. Demidova4, Sergey A. Simanovsky4, Elena N. Slavnova3, Andrey А. Poloznikov3, Andrey P. Polyakov3, Nataliya V. Melnikova1, Alexey A. Dmitriev1, George S. Krasnov1 and Anastasiya V. Snezhkina1 From 11th International Young Scientists School “Systems Biology and Bioinformatics” – SBB-2019 Novosibirsk, Russia. 24-28 June 2019
Abstract Background: Vagal paragangliomas (VPGLs) belong to a group of rare head and neck neuroendocrine tumors. VPGLs arise from the vagus nerve and are less common than carotid paragangliomas. Both diagnostics and therapy of the tumors raise significant challenges. Besides, the genetic and molecular mechanisms behind VPGL pathogenesis are poorly understood. Methods: The collection of VPGLs obtained from 8 patients of Russian population was used in the study. Exome library preparation and high-throughput sequencing of VPGLs were performed using an Illumina technology. Results: Based on exome analysis, we identified pathogenic/likely pathogenic variants of the SDHx genes, frequently mutated in paragangliomas/pheochromocytomas. SDHB variants were found in three patients, whereas SDHD was mutated in two cases. Moreover, likely pathogenic missense variants were also detected in SDHAF3 and SDHAF4 genes encoding for assembly factors for the succinate dehydrogenase (SDH) complex. In a patient, we found a novel variant of the IDH2 gene that was predicted as pathogenic by a series of algorithms used (such as SIFT, PolyPhen2, FATHMM, MutationTaster, and LRT). Additionally, pathogenic/likely pathogenic variants were determined for several genes, including novel genes and some genes previously reported as associated with different types of tumors. Conclusions: Results indicate a high heterogeneity among VPGLs, however, it seems that driver events in most cases are associated with mutations in the SDHx genes and SDH assembly factor-coding genes that lead to disruptions in the SDH complex. Keywords: Vagal paraganglioma, Pathogenic/likely pathogenic mutations, SDHx genes, SHD assembly factor-coding genes, Exome, High-throughput sequencing
* Correspondence: [email protected] 1 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creati
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