The loss of succinate dehydrogenase B expression is frequently identified in hemangioblastoma of the central nervous system

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Succinate dehydrogenase (SDH) is a mitochondrial enzyme that plays an important role in both the Krebs cycle and the electron transport chain. SDH inactivation is associated with tumorigenesis in certain types of tumor. SDH consists of subunits A, B, C and D (SDHA, SDHB, SDHC, and SDHD, respectively). Immunohistochemistry for SDHB is a reliable method for detecting the inactivation of SDH by mutations in SDHA, SDHB, SDHC, SDHD and SDH complex assembly factor 2 ( SDHAF2) genes with high sensitivity and specificity. SDHB immunohistochemistry has been used to examine the inactivation of SDH in various types of tumors. However, data on central nervous system (CNS) tumors are very limited. In the present study, we investigated the loss of SDHB immunoexpression in 90 cases of CNS tumors. Among the 90 cases of CNS tumors, only three cases of hemangioblastoma showed loss of SDHB immunoexpression. We further investigated SDHB immunoexpression in 35 cases of hemangioblastoma and found that 28 (80%) showed either negative or weak-diffuse pattern of SDHB immunoexpression, which suggests the inactivation of SDH. Our results suggest that SDH inactivation may represent an alternative pathway in the tumorigenesis of hemangioblastoma.

Related collections

Most cited references 32

Record: found
Abstract: found
Article: found

Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.

B E Baysal, R Ferrell, J Willett-Brozick … (2000)

Hereditary paraganglioma (PGL) is characterized by the development of benign, vascularized tumors in the head and neck. The most common tumor site is the carotid body (CB), a chemoreceptive organ that senses oxygen levels in the blood. Analysis of families carrying the PGL1 gene, described here, revealed germ line mutations in the SDHD gene on chromosome 11q23. SDHD encodes a mitochondrial respiratory chain protein-the small subunit of cytochrome b in succinate-ubiquinone oxidoreductase (cybS). In contrast to expectations based on the inheritance pattern of PGL, the SDHD gene showed no evidence of imprinting. These findings indicate that mitochondria play an important role in the pathogenesis of certain tumors and that cybS plays a role in normal CB physiology.

0 comments Cited 297 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma.

Lauren Fishbein, Ignaty Leshchiner, Vonn Walter … (2017)

We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine.

0 comments Cited 294 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations.

Katherine A Janeway, Su Kim, Maya Lodish … (2011)

Carney-Stratakis syndrome, an inherited condition predisposing affected individuals to gastrointestinal stromal tumor (GIST) and paraganglioma, is caused by germline mutations in succinate dehydrogenase (SDH) subunits B, C, or D, leading to dysfunction of complex II of the electron transport chain. We evaluated the role of defective cellular respiration in sporadic GIST lacking mutations in KIT or PDGFRA (WT). Thirty-four patients with WT GIST without a personal or family history of paraganglioma were tested for SDH germline mutations. WT GISTs lacking demonstrable SDH genetic inactivation were evaluated for SDHB expression by immunohistochemistry and Western blotting and for complex II activity. For comparison, SDHB expression was also determined in KIT mutant and neurofibromatosis-1-associated GIST, and complex II activity was also measured in SDH-deficient paraganglioma and KIT mutant GIST; 4 of 34 patients (12%) with WT GIST without a personal or family history of paraganglioma had germline mutations in SDHB or SDHC. WT GISTs lacking somatic mutations or deletions in SDH subunits had either complete loss of or substantial reduction in SDHB protein expression, whereas most KIT mutant GISTs had strong SDHB expression. Complex II activity was substantially decreased in WT GISTs. WT GISTs, particularly those in younger patients, have defects in SDH mitochondrial complex II, and in a subset of these patients, GIST seems to arise from germline-inactivating SDH mutations. Testing for germline mutations in SDH is recommended in patients with WT GIST. These findings highlight a potential central role of SDH dysregulation in WT GIST oncogenesis.

0 comments Cited 173 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Se-Hyuk Kim: nsksh@ajou.ac.kr

Jang-Hee Kim: drjhk@ajou.ac.kr

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 10 April 2019

Publication date PMC-release: 10 April 2019

Publication date Collection: 2019

Volume: 9

Electronic Location Identifier: 5873

Affiliations

[1 ]ISNI 0000 0004 0532 3933, GRID grid.251916.8, Department of Neurosurgery, , Ajou University School of Medicine, ; Suwon, 16499 Korea

[2 ]ISNI 0000 0004 0532 3933, GRID grid.251916.8, Department of Pathology, , Ajou University School of Medicine, ; Suwon, 16499 Korea

[3 ]ISNI 0000 0004 0532 3933, GRID grid.251916.8, Department of Medical Genetics, , Ajou University School of Medicine, ; Suwon, 16499 Korea

Article

Publisher ID: 42338

DOI: 10.1038/s41598-019-42338-z

PMC ID: 6458311

PubMed ID: 30971719

SO-VID: d3dacc86-4e17-4c3c-98b8-70453b876765

License:

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 7 September 2018

Date accepted : 27 March 2019

Funding

Funded by: FundRef https://doi.org/10.13039/501100003725, National Research Foundation of Korea (NRF);

Award ID: NRF-2016R1D1A1B02010452

Award Recipient : Se-Hyuk Kim

Funded by: FundRef https://doi.org/10.13039/501100002619, Ajou University;

Award ID: faculty reseach fund2016

Award Recipient : Se-Hyuk Kim

Custom metadata

ScienceOpen disciplines: Uncategorized

Data availability:

ScienceOpen disciplines: Uncategorized

Comments

Comment on this article

scite_

Cited by 6

See all cited by

Most referenced authors 742

See all reference authors

The loss of succinate dehydrogenase B expression is frequently identified in hemangioblastoma of the central nervous system

Read this article at

Abstract

Related collections

Hearing Loss and Restoration

Most cited references 32

Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma.

Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations.

Author and article information

Contributors

Journal

Affiliations

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 318

Cited by 6

Most referenced authors 742