ArticleHuman molecular genetics2010
SDHA is a tumor suppressor gene causing paraganglioma.
Article in Human molecular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 312 papers, 3 of them syntheses that pooled it.
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Who cites it
312 citing papers in PubMed, 3 syntheses or guidelines pooled it, 648 citations in OpenAlex.
- Japan Endocrine Society Clinical Practice Guideline for the Diagnosis and Management of Pheochromocytoma and Paraganglioma 2025.Endocrine journal · 2026Guideline
- Multidisciplinary practice guidelines for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Guideline
- Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: III: Molecular Pathology of Kidney Cancer.The American journal of surgical pathology · 2020Guideline
- Immunohistochemistry and Mutation Analysis ofInternational journal of molecular sciences · 2020Trial
- Are head and neck versus abdominal paragangliomas driven by different single nucleotide events?Journal of applied genetics · 2026Article
- Iron-addicted colorectal cancers exploit heme-complex II axis to resist oxidative cell death.Cell metabolism · 2026Article
- Therapeutic Potential of Cucurbitacin I in Colon Adenocarcinoma Is Mediated by Modulation of SDHA Expression.Journal of cellular and molecular medicine · 2026Article
- Altered Expression of Mitochondrial Succinate Dehydrogenase Subunit D Influences Breast Cancer Progression.International journal of molecular sciences · 2026Article
- The genetics of hypertension.Nature reviews. Nephrology · 2026Review
- Identification of prognostic signatures in pheochromocytomas and paragangliomas based on mitochondrial autophagy and ferroptosis in TCGA and GEO datasets.Discover oncology · 2026Article
- Epigenetic and metabolic rewiring in metastatic pheochromocytomas and paragangliomas driven by SDHB mutations.Communications biology · 2026Article
- Cardiometabolic disease and cardio-oncology: Insights from iPSC models and tissue engineering.Cell reports. Medicine · 2025Review
- Overlapping Presentations and Diverse Genetic Defects Characterize Neuroendocrine Neoplasms in a Mexican Cohort.The Journal of clinical endocrinology and metabolism · 2025Article
- Metabolic Effects of Succinate Dehydrogenase Loss in Cancer.Journal of cellular physiology · 2025Review
- Article
- Epigenetic reprogramming induced by key metabolite depletion is an evolutionarily ancient path to tumorigenesis.Disease models & mechanisms · 2025Article
- Article
- Unveiling the hidden role of SDHA in breast cancer proliferation: a novel therapeutic avenue.Cancer cell international · 2025Article
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- High Succinate peak in Magnetic Resonance Spectroscopy: A Diagnostic Clue for the Leukoencephalopathy Result from Succinate Dehydrogenase Deficiencies.Iranian journal of child neurology · 2025Article
252 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Mitochondrial succinate-coenzyme Q reductase (complex II) consists of four subunits, SDHA, SDHB, SDHC and SDHD. Heterozygous germline mutations in SDHB, SDHC, SDHD and SDHAF2 [encoding for succinate dehydrogenase (SDH) complex assembly factor 2] cause hereditary paragangliomas and pheochromocytomas. Surprisingly, no genetic link between SDHA and paraganglioma/pheochromocytoma syndrome has ever been established. We identified a heterozygous germline SDHA mutation, p.Arg589Trp, in a woman suffering from catecholamine-secreting abdominal paraganglioma. The functionality of the SDHA mutant was assessed by studying SDHA, SDHB, HIF-1alpha and CD34 protein expression using immunohistochemistry and by examining the effect of the mutation in a yeast model. Microarray analyses were performed to study gene expression involved in energy metabolism and hypoxic pathways. We also investigated 202 paragangliomas or pheochromocytomas for loss of heterozygosity (LOH) at the SDHA, SDHB, SDHC and SDHD loci by BAC array comparative genomic hybridization. In vivo and in vitro functional studies demonstrated that the SDHA mutation causes a loss of SDH enzymatic activity in tumor tissue and in the yeast model. Immunohistochemistry and transcriptome analyses established that the SDHA mutation causes pseudo-hypoxia, which leads to a subsequent increase in angiogenesis, as other SDHx gene mutations. LOH was detected at the SDHA locus in the patient's tumor but was present in only 4.5% of a large series of paragangliomas and pheochromocytomas. The SDHA gene should be added to the list of genes encoding tricarboxylic acid cycle proteins that act as tumor suppressor genes and can now be considered as a new paraganglioma/pheochromocytoma susceptibility gene.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.