ArticleCancer discovery2013
Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor.
Article in Cancer discovery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
204 citing papers in PubMed, 1 synthesis or guideline pooled it, 347 citations in OpenAlex.
- Recent Advances in Succinate Dehydrogenase Deficient Gastrointestinal Stromal Tumor Systemic Therapies.Current treatment options in oncology · 2025Pooled it
- Fibroblast growth factor receptor inhibition for succinate dehydrogenase-deficient gastrointestinal stromal tumors: a phase 2 trial.Nature medicine · 2026Trial
- A Phase II Trial of Guadecitabine in Children and Adults with SDH-Deficient GIST, Pheochromocytoma, Paraganglioma, and HLRCC-Associated Renal Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- Linsitinib (OSI-906) for the Treatment of Adult and Pediatric Wild-Type Gastrointestinal Stromal Tumors, a SARC Phase II Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- A Phase II Trial of Vandetanib in Children and Adults with Succinate Dehydrogenase-Deficient Gastrointestinal Stromal Tumor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- Precision therapeutic strategies for advanced gastrointestinal stromal tumors.Cancer metastasis reviews · 2026Review
- Targeting the SETD2-FTO-KIT pathway as a pharmacological strategy for TKI-refractory GIST.Acta pharmaceutica Sinica. B · 2026Article
- Rare Molecular Variants of Gastrointestinal Stromal Tumors (GISTs): Clinical Implications and Overview of Current Evidence.Targeted oncology · 2026Review
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- Impact of mitochondrial reductive stress due to respiratory chain limitation on cancer via posttranslational modifications.Redox biology · 2026Review
- Tumor cell intrinsic mechanisms of immune escape.Cell communication and signaling : CCS · 2026Review
- Article
- Metabolic permissiveness: how tissue context shapes cancer.Genes & development · 2026Review
- Epigenetic and metabolic rewiring in metastatic pheochromocytomas and paragangliomas driven by SDHB mutations.Communications biology · 2026Article
- 3D Chromatin Architecture During Early Development: New Methods and New Findings.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Review
- Olverembatinib, a multikinase inhibitor that modulates lipid metabolism, in advanced succinate dehydrogenase-deficient gastrointestinal stromal tumors: a phase 1b study and translational research.Signal transduction and targeted therapy · 2025Article
- Metabolic Effects of Succinate Dehydrogenase Loss in Cancer.Journal of cellular physiology · 2025Review
- Oleocanthal as a Multifunctional Anti-Cancer Agent: Mechanistic Insights, Advanced Delivery Strategies, and Synergies for Precision Oncology.International journal of molecular sciences · 2025Review
- Comprehensive metabolomic and epigenomic characterization of microsatellite stable BRAF-mutated colorectal cancer.Oncogene · 2025Article
144 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
29 authors at 8 institutions in 2 countries.
Funding
Abstract
Gastrointestinal stromal tumors (GIST) harbor driver mutations of signal transduction kinases such as KIT, or, alternatively, manifest loss-of-function defects in the mitochondrial succinate dehydrogenase (SDH) complex, a component of the Krebs cycle and electron transport chain. We have uncovered a striking divergence between the DNA methylation profiles of SDH-deficient GIST (n = 24) versus KIT tyrosine kinase pathway-mutated GIST (n = 39). Infinium 450K methylation array analysis of formalin-fixed paraffin-embedded tissues disclosed an order of magnitude greater genomic hypermethylation relative to SDH-deficient GIST versus the KIT-mutant group (84.9 K vs. 8.4 K targets). Epigenomic divergence was further found among SDH-mutant paraganglioma/pheochromocytoma (n = 29), a developmentally distinct SDH-deficient tumor system. Comparison of SDH-mutant GIST with isocitrate dehydrogenase-mutant glioma, another Krebs cycle-defective tumor type, revealed comparable measures of global hypo- and hypermethylation. These data expose a vital connection between succinate metabolism and genomic DNA methylation during tumorigenesis, and generally implicate the mitochondrial Krebs cycle in nuclear epigenomic maintenance.
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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.