Mutation profiling in eight cases of vagal paragangliomas.

Autor: Kudryavtseva AV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia. rhizamoeba@mail.ru., Kalinin DV; Vishnevsky Institute of Surgery, Ministry of Health of the Russian Federation, Moscow, Russia., Pavlov VS; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Savvateeva MV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Fedorova MS; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Pudova EA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Kobelyatskaya AA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Golovyuk AL; Vishnevsky Institute of Surgery, Ministry of Health of the Russian Federation, Moscow, Russia., Guvatova ZG; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Razmakhaev GS; National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia., Demidova TB; A. N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, Moscow, Russia., Simanovsky SA; A. N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, Moscow, Russia., Slavnova EN; National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia., Poloznikov AА; National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia., Polyakov AP; National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia., Melnikova NV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Dmitriev AA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Krasnov GS; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Snezhkina AV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Jazyk: angličtina
Zdroj: BMC medical genomics [BMC Med Genomics] 2020 Sep 18; Vol. 13 (Suppl 8), pp. 115. Date of Electronic Publication: 2020 Sep 18.
DOI: 10.1186/s12920-020-00763-4
Abstrakt: 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.
Databáze: MEDLINE
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