scholarly journals Alternative splicing isoform in succinate dehydrogenase complex, subunit C causes downregulation of succinate-coenzyme Q oxidoreductase activity in mitochondria

2014 ◽  
Vol 9 (1) ◽  
pp. 330-334 ◽  
Author(s):  
NANA SATOH ◽  
CHIKAKO YOKOYAMA ◽  
NORIAKI ITAMURA ◽  
YOSHIHARU MIYAJIMA-NAKANO ◽  
HISASHI HISATOMI
Keyword(s):  
Alternative Splicing ◽  
Succinate Dehydrogenase ◽  
Coenzyme Q ◽  
Oxidoreductase Activity ◽  
Subunit C ◽  
Succinate Dehydrogenase Complex ◽  
Succinate Dehydrogenase Complex Subunit ◽  
Dehydrogenase Complex

scholarly journals Measurements of Plasma Methoxytyramine, Normetanephrine, and Metanephrine as Discriminators of Different Hereditary Forms of Pheochromocytoma

2011 ◽  
Vol 57 (3) ◽  
pp. 411-420 ◽  
Author(s):  
Graeme Eisenhofer ◽  
Jacques WM Lenders ◽  
Henri Timmers ◽  
Massimo Mannelli ◽  
Stefan K Grebe ◽  
...  
Keyword(s):  
Succinate Dehydrogenase ◽  
Plasma Concentrations ◽  
Neurofibromatosis Type ◽  
Underlying Disease ◽  
Plasma Catecholamine ◽  
Von Hippel Lindau ◽  
Men 2 ◽  
Succinate Dehydrogenase Complex ◽  
Succinate Dehydrogenase Complex Subunit ◽  
Dehydrogenase Complex

BACKGROUND Pheochromocytomas are rare catecholamine-producing tumors derived in more than 30% of cases from mutations in 9 tumor-susceptibility genes identified to date, including von Hippel-Lindau tumor suppressor (VHL); succinate dehydrogenase complex, subunit B, iron sulfur (Ip) (SDHB); and succinate dehydrogenase complex, subunit D, integral membrane protein (SDHD). Testing of multiple genes is often undertaken at considerable expense before a mutation is detected. This study assessed whether measurements of plasma metanephrine, normetanephrine, and methoxytyramine, the O-methylated metabolites of catecholamines, might help to distinguish different hereditary forms of the tumor. METHODS Plasma concentrations of O-methylated metabolites were measured by liquid chromatography with electrochemical detection in 173 patients with pheochromocytoma, including 38 with multiple endocrine neoplasia type 2 (MEN 2), 10 with neurofibromatosis type 1 (NF1), 66 with von Hippel-Lindau (VHL) syndrome, and 59 with mutations of SDHB or SDHD. RESULTS In contrast to patients with VHL, SDHB, and SDHD mutations, all patients with MEN 2 and NF1 presented with tumors characterized by increased plasma concentrations of metanephrine (indicating epinephrine production). VHL patients usually showed solitary increases in normetanephrine (indicating norepinephrine production), whereas additional or solitary increases in methoxytyramine (indicating dopamine production) characterized 70% of patients with SDHB and SDHD mutations. Patients with NF1 and MEN 2 could be discriminated from those with VHL, SDHB, and SDHD gene mutations in 99% of cases by the combination of normetanephrine and metanephrine. Measurements of plasma methoxytyramine discriminated patients with SDHB and SDHD mutations from those with VHL mutations in an additional 78% of cases. CONCLUSIONS The distinct patterns of plasma catecholamine O-methylated metabolites in patients with hereditary pheochromocytoma provide an easily used tool to guide cost-effective genotyping of underlying disease-causing mutations.

scholarly journals The emerging clinical relevance of genomic profiling in neuroendocrine tumours

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guney Isa Burak ◽  
Sonmezler Ozge ◽  
Mujde Cem ◽  
Buyukdereli Gulgun ◽  
Dogruca Yapar Zeynep ◽  
...  
Keyword(s):  
Succinate Dehydrogenase ◽  
Peripheral Blood ◽  
Germ Line ◽  
Genomic Profiling ◽  
Liquid Biopsies ◽  
Blood Samples ◽  
Ffpe Tissues ◽  
Succinate Dehydrogenase Complex ◽  
Succinate Dehydrogenase Complex Subunit ◽  
Dehydrogenase Complex

Abstract Background Neuroendocrine tumours (NETs) arise from hormone-producing or nervous system cells and can develop from anywhere in the body. They have heterogeneous origins from skin to gastrointestinal track and a complicated histology. Thus, there is an inevitable need for genomic profiling to determine the exact genetics of each tumour for prognosis and treatment strategies to overcome the disease’s complexity. For this purpose, next-generation-sequencing (NGS) is the most reliable methodology for both germ-line and somatic studies to make a clinical diagnosis. In this study, we analyse liquid biopsies, formalin fixed paraffin embedded (FFPE) tissues, and peripheral blood samples for their ability to provide information for actionability. Methods A customized multi-gene panel comprised of Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB), Succinate Dehydrogenase Complex Subunit C (SDHC), Cell Division Cycle 73(CDC73), Calcium Sensing Receptor (CASR), Platelet Derived Growth Factor Receptor Alpha (PDGFRA), Succinate Dehydrogenase Complex Flavoprotein Subunit A (SDHA), Ret Proto-Oncogene (RET), Succinate Dehydrogenase Complex Assembly Factor 2(SDHAF2), Menin 1(MEN1), Succinate Dehydrogenase Complex Subunit D (SDHD), MYC Associated Factor X (MAX) and Protein Kinase CAMP-Dependent Type I Regulatory Subunit Alpha (PRKAR1A) genes was constructed to assess multiple specimen types including: 3 liquid biopsies, 6 FFPE tissues, and 26 peripheral blood samples from 35 unique NET patients. Quality-control and bioinformatics analyses were performed using QCI-Analyze and QCI-Interpret. Results The three liquid biopsies and the 6 FFPE tissue samples were evaluated for somatic mutations; while the 26 peripheral blood samples were analysed using the germ-line pipeline. Five (55.6%) of the nine patients that were studied for somatic changes carried actionable mutations related to therapy sensitivities. Through the germ-line studies, we observed a 50% positivity rate for disease predisposition with 16 variants classified according to ACMG (American College of Medical Genetics) Standards and Guidelines. Conclusions Genomic profiling medicine is an emerging area of clinical oncology and has become crucial for disease and patient management by providing a precision approach; this is especially true for rare diseases including rare cancers such as NETs. Notably, this study emphasized the relevance of multiple distinctive biological sample types for use in the genetic testing of cancers to help with the choice of therapy to maximize the likelihood of a positive clinical outcome.

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