Genetic changes in the FH gene cause vagal paraganglioma.

Autor:	Snezhkina AV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Pavlov VS; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Kalinin DV; Vishnevsky Institute of Surgery, Ministry of Health of the Russian Federation, Moscow, Russia., Pudova EA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Krasnov GS; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Ayupova AF; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Kobelyatskaya AA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Dmitriev AA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Atiakshin DA; Scientific and Educational Resource Center 'Innovative Technologies of Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis', RUDN University, Moscow, Russia., Fedorova MS; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Kudryavtseva AV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2024 Apr 24; Vol. 15, pp. 1381093. Date of Electronic Publication: 2024 Apr 24 (Print Publication: 2024).
DOI:	10.3389/fendo.2024.1381093
Abstrakt:	Vagal paraganglioma (VPGL) is a rare neuroendocrine tumor that originates from the paraganglion associated with the vagus nerve. VPGLs present challenges in terms of diagnostics and treatment. VPGL can occur as a hereditary tumor and, like other head and neck paragangliomas, is most frequently associated with mutations in the SDHx genes. However, data regarding the genetics of VPGL are limited. Herein, we report a rare case of a 41-year-old woman with VPGL carrying a germline variant in the FH gene. Using whole-exome sequencing, a variant, FH p.S249R, was identified; no variants were found in other PPGL susceptibility and candidate genes. Loss of heterozygosity analysis revealed the loss of the wild-type allele of the FH gene in the tumor. The pathogenic effect of the p.S249R variant on FH activity was confirmed by immunohistochemistry for S-(2-succino)cysteine (2SC). Potentially deleterious somatic variants were found in three genes, SLC7A7 , ZNF225 , and MED23 . The latter two encode transcriptional regulators that can impact gene expression deregulation and are involved in tumor development and progression. Moreover, FH -mutated VPGL was characterized by a molecular phenotype different from SDHx -mutated PPGLs. In conclusion, the association of genetic changes in the FH gene with the development of VPGL was demonstrated. The germline variant FH : p.S249R and somatic deletion of the second allele can lead to biallelic gene damage that promotes tumor initiation. These results expand the clinical and mutation spectra of FH -related disorders and improve our understanding of the molecular genetic mechanisms underlying the pathogenesis of VPGL. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Snezhkina, Pavlov, Kalinin, Pudova, Krasnov, Ayupova, Kobelyatskaya, Dmitriev, Atiakshin, Fedorova and Kudryavtseva.)
Databáze:	MEDLINE
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