Mutation profiling in eight cases of vagal paragangliomas
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 molecula...
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doaj-d3d667cb88dc4d0782b8c0c21e300aac2021-04-02T10:56:29ZengBMCBMC Medical Genomics1755-87942020-09-0113S811110.1186/s12920-020-00763-4Mutation profiling in eight cases of vagal paragangliomasAnna V. Kudryavtseva0Dmitry V. Kalinin1Vladislav S. Pavlov2Maria V. Savvateeva3Maria S. Fedorova4Elena A. Pudova5Anastasiya A. Kobelyatskaya6Alexander L. Golovyuk7Zulfiya G. Guvatova8George S. Razmakhaev9Tatiana B. Demidova10Sergey A. Simanovsky11Elena N. Slavnova12Andrey А. Poloznikov13Andrey P. Polyakov14Nataliya V. Melnikova15Alexey A. Dmitriev16George S. Krasnov17Anastasiya V. Snezhkina18Engelhardt Institute of Molecular Biology, Russian Academy of SciencesVishnevsky Institute of Surgery, Ministry of Health of the Russian FederationEngelhardt Institute of Molecular Biology, Russian Academy of SciencesEngelhardt Institute of Molecular Biology, Russian Academy of SciencesEngelhardt Institute of Molecular Biology, Russian Academy of SciencesEngelhardt Institute of Molecular Biology, Russian Academy of SciencesEngelhardt Institute of Molecular Biology, Russian Academy of SciencesVishnevsky Institute of Surgery, Ministry of Health of the Russian FederationEngelhardt Institute of Molecular Biology, Russian Academy of SciencesNational Medical Research Radiological Center, Ministry of Health of the Russian FederationA. N. Severtsov Institute of Ecology and Evolution, Russian Academy of SciencesA. N. Severtsov Institute of Ecology and Evolution, Russian Academy of SciencesNational Medical Research Radiological Center, Ministry of Health of the Russian FederationNational Medical Research Radiological Center, Ministry of Health of the Russian FederationNational Medical Research Radiological Center, Ministry of Health of the Russian FederationEngelhardt Institute of Molecular Biology, Russian Academy of SciencesEngelhardt Institute of Molecular Biology, Russian Academy of SciencesEngelhardt Institute of Molecular Biology, Russian Academy of SciencesEngelhardt Institute of Molecular Biology, Russian Academy of SciencesAbstract 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.http://link.springer.com/article/10.1186/s12920-020-00763-4Vagal paragangliomaPathogenic/likely pathogenic mutationsSDHx genesSHD assembly factor-coding genesExomeHigh-throughput sequencing |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna V. Kudryavtseva Dmitry V. Kalinin Vladislav S. Pavlov Maria V. Savvateeva Maria S. Fedorova Elena A. Pudova Anastasiya A. Kobelyatskaya Alexander L. Golovyuk Zulfiya G. Guvatova George S. Razmakhaev Tatiana B. Demidova Sergey A. Simanovsky Elena N. Slavnova Andrey А. Poloznikov Andrey P. Polyakov Nataliya V. Melnikova Alexey A. Dmitriev George S. Krasnov Anastasiya V. Snezhkina |
spellingShingle |
Anna V. Kudryavtseva Dmitry V. Kalinin Vladislav S. Pavlov Maria V. Savvateeva Maria S. Fedorova Elena A. Pudova Anastasiya A. Kobelyatskaya Alexander L. Golovyuk Zulfiya G. Guvatova George S. Razmakhaev Tatiana B. Demidova Sergey A. Simanovsky Elena N. Slavnova Andrey А. Poloznikov Andrey P. Polyakov Nataliya V. Melnikova Alexey A. Dmitriev George S. Krasnov Anastasiya V. Snezhkina Mutation profiling in eight cases of vagal paragangliomas BMC Medical Genomics Vagal paraganglioma Pathogenic/likely pathogenic mutations SDHx genes SHD assembly factor-coding genes Exome High-throughput sequencing |
author_facet |
Anna V. Kudryavtseva Dmitry V. Kalinin Vladislav S. Pavlov Maria V. Savvateeva Maria S. Fedorova Elena A. Pudova Anastasiya A. Kobelyatskaya Alexander L. Golovyuk Zulfiya G. Guvatova George S. Razmakhaev Tatiana B. Demidova Sergey A. Simanovsky Elena N. Slavnova Andrey А. Poloznikov Andrey P. Polyakov Nataliya V. Melnikova Alexey A. Dmitriev George S. Krasnov Anastasiya V. Snezhkina |
author_sort |
Anna V. Kudryavtseva |
title |
Mutation profiling in eight cases of vagal paragangliomas |
title_short |
Mutation profiling in eight cases of vagal paragangliomas |
title_full |
Mutation profiling in eight cases of vagal paragangliomas |
title_fullStr |
Mutation profiling in eight cases of vagal paragangliomas |
title_full_unstemmed |
Mutation profiling in eight cases of vagal paragangliomas |
title_sort |
mutation profiling in eight cases of vagal paragangliomas |
publisher |
BMC |
series |
BMC Medical Genomics |
issn |
1755-8794 |
publishDate |
2020-09-01 |
description |
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. |
topic |
Vagal paraganglioma Pathogenic/likely pathogenic mutations SDHx genes SHD assembly factor-coding genes Exome High-throughput sequencing |
url |
http://link.springer.com/article/10.1186/s12920-020-00763-4 |
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