Gene of the month: SDH

Aldera, Alessandro Pietro; Govender, Dhirendra

doi:10.1136/jclinpath-2017-204677

Cited by 32 publications

(34 citation statements)

References 49 publications

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“…Succinate dehydrogenase protein C (SDHC) is part of a family of metabolic enzymes that function in the citric acid cycle and electron transport chains. Germline inactivating mutations in SDHC result in accumulation of succinate and are associated with paragangliomas, renal cell carcinomas, and gastrointestinal stromal tumors ( 35 ). While RECQL4 and SDHC have been studied in the context of breast cancer, they have not been previously considered in African populations.…”

Section: Discussionmentioning

confidence: 99%

Next-generation sequencing identifies recurrent copy number variations in invasive breast carcinomas from Ghana

et al. 2020

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African and African American (AA) women have a higher incidence of triple negative breast cancers (TNBC) with high histological grade and aggressive clinical behavior, but the reasons are not fully understood. We recently found that the oncogenic protein EZH2 is overexpressed in Ghanaian breast cancer, with 16% of the tumors expressing cytoplasmic EZH2. Understanding the molecular underpinnings of these aggressive tumors lead to the identification of potential targetable oncogenic drivers. We characterized the copy number variations of 11 Ghanaian breast tumors by targeted multiplexed PCR-based DNA next generation sequencing (NGS) of over 130 cancer-relevant genes. While the DNA quality was not optimal for mutation analysis, 90% of the tumors had frequent recurrent copy number alterations (CNAs) of 17 genes: SDHC, RECQL4, TFE3, BCL11A, BCL2L1, PDGFRA, DEK, SMUG1, AKT3, SMARCA4, VHL, KLF6, CCNE1, G6PD, FGF3, ABL1, and CCND1 , with the top oncogenic functions being mitotic G1–G1/S phase regulation, gene transcription, apoptosis, and PI3K/AKT pathway. The most common recurrent high level CNAs were gains of RECQL4 and SDHC , in 50% and 60% of cases, respectively. Network analyses revealed a significant predicted interaction among 12 of the 17 (70.6%) genes with high level CNAs (p=5.7E-07), which was highly correlated with EZH2 expression (r=0.4–0.75). By immunohistochemistry, RECQL4 and SDHC proteins were upregulated in 53 of 86 (61.6%) and 48 of 86 (56%) of Ghanaian invasive carcinomas tissue samples. In conclusion, our data show that invasive carcinomas from Ghana exhibit recurrent CNAs in 17 genes with functions in oncogenic pathways including PI3K/AKT and G1–G1/S regulation, which may have implications for the biology and treatment of invasive carcinomas in African and AA women.

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Section: Discussionmentioning

confidence: 99%

Next-generation sequencing identifies recurrent copy number variations in invasive breast carcinomas from Ghana

et al. 2020

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“…Succinate dehydrogenase complex are nuclear‐encoded genes whose proteins form the succinate dehydrogenase complex (complex II) in the electron transport chain , Fig. .…”

Section: Succinate Dehydrogenase Function In Mitochondrial Disease Anmentioning

confidence: 99%

Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma

et al. 2019

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Pheochromocytoma and paraganglioma (PPGL) are rare tumours and at least 30% are part of hereditary syndromes. Approximately 20% of hereditary PPGL are caused by pathogenic germ line variants in genes of the succinate dehydrogenase complex (SDHx), TMEM127 or MAX. Herein we present guidelines regarding genetic testing of family members and their surveillance based on a thorough literature review. All cases of PPGL are recommended genetic testing for germ line variants regardless of patient and family characteristics. At minimum, FH, NF1, RET, SDHB, SDHD and VHL should be tested. In addition, testing of MEN1, SDHA, SDHAF2, SDHC, TMEM127 and MAX is recommended. Healthy first‐degree relatives (and second‐degree relatives in the case of SDHD and SDHAF2 which are maternally imprinted) should be offered carrier testing. Carriers of pathogenic variants should be offered surveillance with annual biochemical measurements of methoxy‐catecholamines and bi‐annual rapid whole‐body magnetic resonance imaging and clinical examination. Surveillance should start 5 years before the earliest age of onset in the family and thus only children eligible for surveillance should be offered pre‐symptomatic genetic testing. The surveillance of children younger than 15 years needs to be individually designed. Our guidelines will provide a framework for patient management with the possibility to follow outcome via national registries and/or follow‐up studies. Together with improved insights into the disease, this may enable optimisation of the surveillance scheme in order to minimise both anxiety and medical complications while ensuring early disease detection.

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“…Succinic dehydrogenase subunit A (SDHA), a flavoprotein with FAD as cofactor, is a nuclear encoded and catalytic subunit of Complex II (succinate dehydrogenase) which oxidizes succinate to fumarate in the Kreb's cycle and transfers electrons to ubiquinone in the mitochondrial electron transport chain [115] .…”

Section: Succinic Dehydrogenase Subunit a Deficiency (Omim #252011)mentioning

confidence: 99%

Riboflavin metabolism: role in mitochondrial function

Balasubramaniam¹,

Yaplito‐Lee²

2020

jtgg

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Riboflavin, known as vitamin B2, a water-soluble vitamin, is an essential nutrient in vertebrates, hence adequate dietary intake is imperative. Riboflavin plays a role in a variety of metabolic pathways, serving primarily as an integral component of its crucial biologically active forms, the flavocoenzymes flavin adenine dinucleotide and flavin mononucleotide. These flavocoenzymes ensure the functionality of numerous flavoproteins including dehydrogenases, oxidases, monooxygenases, and reductases, which play pivotal roles in mitochondrial electron transport chain, β-oxidation of fatty acids, redox homeostasis, citric acid cycle, branched-chain amino acid catabolism, chromatin remodeling, DNA repair, protein folding, and apoptosis. Unsurprisingly, impairment of flavin homeostasis in humans has been linked to various diseases including neuromuscular and neurological disorders, abnormal fetal development, and cardiovascular diseases. This review presents an overview of riboflavin metabolism, its role in mitochondrial function, primary and secondary flavocoenzyme defects associated with mitochondrial dysfunction, and the role of riboflavin supplementation in these conditions.

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Gene of the month: SDH

Cited by 32 publications

References 49 publications

Next-generation sequencing identifies recurrent copy number variations in invasive breast carcinomas from Ghana

Next-generation sequencing identifies recurrent copy number variations in invasive breast carcinomas from Ghana

Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma

Riboflavin metabolism: role in mitochondrial function

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