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SDH Mutations Establish a Hypermethylator Phenotype in Paraganglioma
Open accessAbstract
Paragangliomas are neuroendocrine tumors frequently associated with mutations in RET, NF1, VHL, and succinate dehydrogenase (SDHx) genes. Methylome analysis of a large paraganglioma cohort identified three stable clusters, associated with distinct clinical features and mutational status. SDHx-related tumors displayed a hypermethylator phenotype, associated with downregulation of key genes involved in neuroendocrine differentiation. Succinate accumulation in SDH-deficient mouse chromaffin cells led to DNA hypermethylation by inhibition of 2-OG-dependent histone and DNA demethylases and established a migratory phenotype reversed by decitabine treatment. Epigenetic silencing was particularly severe in SDHB-mutated tumors, potentially explaining their malignancy. Finally, inactivating FH mutations were identified in the only hypermethylated tumor without SDHx mutations. These findings emphasize the interplay between the Krebs cycle, epigenomic changes, and cancer.
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“Like D-2HG, fumarate and succinate accumulation can inhibit some αKG-dependent dioxygenases, resulting in hypermethylation of DNA and histones in tumors exhibiting loss of FH or SDH (Hoekstra et al., 2015; Letouze et al., 2013; Xiao et al., 2012).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Letouze et al., 2013
In the citing paper
“In cancer cells, mutations in succinate dehydrogenase subunit B (SDHB) cause susceptibility to familial pheochromocytoma99 and familial paraganglioma100 as well as gastrointestinal stromal tumors101.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [100]
In the citing paper
“As succinate accumulates via the inhibition of the 2-OGDD enzyme, epigenetic modification acts in the process of cell transformation into a hypermethylated phenotype100.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [100]
In the citing paper
“Although additional studies are needed, ample experimental data support the recognition of R-2-HG, succinate, and fumarate as oncometabolites.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [100]
In the citing paper
“Several studies have shown that SDH-deficient cells exhibit increased tumorigenesis and that this increase is reversed by the addition of α-KG, supporting the idea that succinate accumulation contributes to tumorigenesis through epigenetic modification100.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [100]
In the citing paper
“Tumors that exhibit SDH- and FH loss share a number of phenotypic features that are consistent with dioxygenase inhibition, among which is a characteristic global increase in DNA methylation (Killian et al., 2013; Letouze et al., 2013; Xiao et al., 2012), as well as elevated levels of HIF1α (Selak et al., 2005).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Letouze et al., 2013
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Is There a Therapeutic Window for Metabolism-Based Cancer Therapies?
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“TCA cycle intermediates succinate and fumarate tend to accumulate as a result of mutations in succinate dehydrogenase or fumarate hydratase, which lead to an upregulation of EMTrelated genes (100, 101).”
BackgroundTKI Treatment Sequencing in Advanced Gastrointestinal Stromal Tumors
Khosroyani, H. M., Klug, L. R., & Heinrich, M. C. (2023) · Drugs · doi:10.1007/s40265-022-01820-1 · Cited by 23
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“Finally, DNA hypermethylation has also been identified in tumors with FH mutations.(109,121)”
Exploring the association of succinate dehydrogenase complex mutations with lymphoid malignancies
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Fliedner, S. M. J., Brabant, G. E., & Lehnert, H. (2018) · Cell and Tissue Research · doi:10.1007/s00441-017-2760-3 · Cited by 22
“Similarly, SDHB and SDHD PGLs contain fewer secretory granules t han RET and NF1 PHEOs (own unpub l i shed observation).”
BackgroundInfluentialRodent models of pheochromocytoma, parallels in rodent and human tumorigenesis
Lussey‐Lepoutre, C., Buffet, A., Morin, A., Goncalves, J., & Favier, J. (2018) · Cell and Tissue Research · doi:10.1007/s00441-018-2797-y · Cited by 23
“related animal model, our lab recently generated an allografted mouse model by subcutaneous injection of immortalized mouse chromaffin cells (imCC) (Letouze et al. 2013) carrying a homozygous knockout of the Sdhb gene into the fat-pad of female NMRI-nu mice (Lussey-Lepoutre et al.”
BackgroundMethodInfluentialSelf-citationBiamonti, G., Maita, L., & Montecucco, A. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00408 · Cited by 22
“Also inactivating mutations in fumarate hydratase (FH) and succinate dehydrogenase (SDH) genes are causative of a subset of tumors (19) and produce fumarate and succinate accumulation to millimolar levels, far in excess of physiological concentrations (106, 107).”
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Potential Biomarkers of Metastasizing Paragangliomas and Pheochromocytomas
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“, fumarate hydratase, isocitrate dehydrogenase, and succinate dehydrogenase have been recognized to associate with EMT activation [34, 35].”
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“PPGLs are grouped in clusters based on their transcriptional profile [9] and tumorigenic mechanism underlying their aetiology [10].”
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A unique model for SDH-deficient GIST: an endocrine-related cancer
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Targeting pheochromocytoma/paraganglioma with polyamine inhibitors
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“Other genes and pathways implicated in CIMP include SDHB [succinate dehydrogenase complex iron sulfur subunit B] in paraganglioma [7], KRAS [KRAS proto-oncogene, GTPase], and activating BRAF [B-Raf proto-oncogene, serine/threonine kinase] mutations in colorectal cancer [8, 9].”
BackgroundBechmann, N., & Eisenhofer, G. (2021) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-1526-5263 · Cited by 21
“Especially oncometabolite-driven tumors, such as PPGLs of the TCA cycle-related cluster 1, and here in particular tumors with SDHB mutations show hypermethylation [57, 58].”
BackgroundEpigenome modifiers and metabolic rewiring: New frontiers in therapeutics
Ferrari, A., Longo, R., Silva, R., Mitro, N., Caruso, D., De Fabiani, E., & Crestani, M. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.08.008 · Cited by 19
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“Loss of FH and SDH has been specifically found to drive cancer progression through an accumulation of nuclear fumarate and succinate, leading to inhibition of demethylation enzymes in the nucleus [76, 77].”
Transcriptome Analysis of lncRNAs in Pheochromocytomas and Paragangliomas
Job, S., Georges, A. B., Burnichon, N., Buffet, A., Amar, L., Bertherat, J. Y., Bouatia‐Naji, N., de Reyniès, A., Drui, D., Lussey‐Lepoutre, C., et al. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz168 · Cited by 19
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“Similarly, paragangliomas, pheochromocytomas and GISTs associated with germline mutation of SDHB, SDHC and SDHD have been previously shown to exhibit CIMP in comparison to tumors caused by mutations in other genes [23, 24].”
BackgroundInfluentialThe Interplay between Dysregulated Metabolism and Epigenetics in Cancer
Bassal, M. A. (2023) · Biomolecules · doi:10.3390/biom13060944 · Cited by 19
Rewiring of RNA methylation by the oncometabolite fumarate in renal cell carcinoma
Fitzsimmons, C. M., Mandler, M. D., Lunger, J. C., Chan, D., Maligireddy, S. S., Schmiechen, A. C., Gamage, S. T., Link, C. N., Jenkins, L. M. M., Chan, K. C., et al. (2024) · NAR Cancer · doi:10.1093/narcan/zcae004 · Cited by 18
Control of topoisomerase II activity and chemotherapeutic inhibition by TCA cycle metabolites
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DNA methylation in adult diffuse gliomas
Leblanc, V., & Marra, M. A. (2016) · Briefings in Functional Genomics · doi:10.1093/bfgp/elw019 · Cited by 20
Chen, C.-L., Ishihara, T., Pal, S., Huang, W., Ogasawara, E., Chang, C., & Ishihara, N. (2024) · Mitochondrion · doi:10.1016/j.mito.2024.101952 · Cited by 17
Moonlighting Enzymes at the Interface Between Metabolism and Epigenetics
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“2005), DNA hypermethylation (Letouzé et al. 2013) and activation of angiogenesis.”
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“Finally, the pervasive DNA hypermethylation results in transcriptional silencing of multiple tumor suppressor genes (33, 37, 68).”
BackgroundTheVHL gene is epigenetically inactivated in pheochromocytomas and abdominal paragangliomas
Stenman, A., Kiss, N. B., Caramuta, S., Sulaiman, L. R., Svahn, F., Bäckdahl, M., Höög, A., Juhlin, C. C., & Larsson, C. (2013) · Epigenetics · doi:10.4161/epi.26686 · Cited by 17
“Studies of DNA methylation have revealed CpG hypermethylator phenotypes in PGLs carrying a SDHB,(12,13) or SDHx mutation as was also demonstrated in a mouse model.(14) However, possible somatic inactivation of the PCC/PGL predisposing genes by promoter methylation has so far not been fully determined.”
BackgroundFacchin, C., Pérez-Liva, M., Garofalakis, A., Viel, T., Certain, A., Balvay, D., Yoganathan, T., Woszczyk, J., Sousa, K. D., Sourdon, J., et al. (2020) · Theranostics · doi:10.7150/thno.40687 · Cited by 19
“In the tumor model used here, the Sdhb-/- cells are in a succinate-induced pseudohypoxic state, in which there is stabilization of HIF-2α [39, 52], but grow inside PPGL tumors which receive a consistent blood supply.”
BackgroundSelf-citationHypothesis: Why Different Types of SDH Gene Variants Cause Divergent Tumor Phenotypes
Bayley, J., & Devilee, P. (2022) · Genes · doi:10.3390/genes13061025 · Cited by 18
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“Genes conferring susceptibility for cluster 1 PPGLs also include SDH subunit genes and FH that result in production of the oncometabolites succinate or fumarate, which inhibit α -ketoglutarate-dependent enzymes and thereby induce HIF signaling and global epigenetic modifications [113, 114].”
BackgroundFumarate Metabolic Signature for the Detection of Reed Syndrome in Humans
Casey, R. T., McLean, M. A., Challis, B., McVeigh, T. P., Warren, A. Y., Mendil, L., Houghton, R., de Sanctis, S., Kosmoliaptsis, V., Sandford, R. N., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1729 · Cited by 16
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“These mutations cause dysfunction of the TCA cycle and accumulation of metabolic intermediates, modifying the function of cancer cells [20,21].”
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Precision Medicine in Phaeochromocytoma and Paraganglioma
Winzeler, B. F., Challis, B., & Casey, R. T. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11111239 · Cited by 17
“Demethylating agents may have therapeutic benefit in Cluster 1 mutated PPGL because of the hypermethylation phenotype promoted by mutations in Kreb’s cycle genes [70].”
BackgroundTranscriptional regulation of metabolism in disease: From transcription factors to epigenetics
Hawkins, L. J., Al-attar, R., & Storey, K. B. (2018) · PeerJ · doi:10.7717/peerj.5062 · Cited by 17
“SDH mutations in paragangliomas show hypermethylation in gene promoters, particularly associated with genes involved in neuroendocrine differentiation, leading to their downregulation (Letouzé et al., 2013).”
BackgroundNutritional and metabolic signalling through GPCRs
Pardella, E., Ippolito, L., Giannoni, E., & Chiarugi, P. (2022) · FEBS Letters · doi:10.1002/1873-3468.14441 · Cited by 18
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“It has been shown that mutations in FH and SDHB are associated with hypermethylator phenotypes [19, 20].”
BackgroundUsing mass spectrometry imaging to visualize age-related subcellular disruption
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“Of particular significance is succinate, a product of the demethyation reaction that competitively inhibits JmjC activity in vitro , and whose accumulation has been correlated with decreased JmjC-mediated histone demethylation in vivo 5–7 .”
Wang, Z., Chen, H., Xue, L., He, W., Shu, W., Wu, H., & Wang, Z. (2021) · Translational Oncology · doi:10.1016/j.tranon.2021.101146 · Cited by 15
“The SDHx mutations in pheochromocytomas (PCCs) and PGLs lead to elevated succinate levels that mediate inhibition of 2-OG-dependent histone and DNA demethylases, thereby causing a CpG island methylator phenotype (CIMP), defined as the methylation of CpG islands of multiple tumor-suppressor genes (TSGs) [16].”
BackgroundMitochondrial substrates in cancer: Drivers or passengers?
Kruspig, B., Zhivotovsky, B., & Gogvadze, V. G. (2014) · Mitochondrion · doi:10.1016/j.mito.2014.08.007 · Cited by 15
Clinical and molecular markers guide the genetics of pheochromocytoma and paraganglioma
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Self-citationDong, Y., Huang, Y., Fan, C., Wang, L., Zhang, R., Li, W., Guo, Z., Wang, D., & Zheng, Z. J. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03731-7 · Cited by 14
Jaitovich, A. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00292.2022 · Cited by 16
Mellid, S., Gil, E., Letón, R., Caleiras, E. J., Honrado, E., Richter, S., Palacios, N., Lahera, M., Galofré, J. C., López‐Fernández, A., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1070074 · Cited by 14
“Another molecular marker described for DLSTmutated tumours is the low level of 5-hmC nuclear staining (21), similar to the observed in SDH-mutated PPGLs (25).”
BackgroundZhong, X., Su, T., Yang, Y., Ye, L., Jiang, L., Qi, Y., Xie, J., Jiang, Y., Zhou, W., Zhang, C., et al. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad149 · Cited by 15
A high-throughput analysis of the IDH1(R132H) protein expression in pituitary adenomas
Casar‐Borota, O., Øystese, K. A., Sundström, M., Melchior, L. C., & POPOVIC, V. M. (2016) · Pituitary · doi:10.1007/s11102-016-0720-7 · Cited by 14
“Deficiencies in other enzymes participating in the Krebs cycle, in particular deficiency of the succinate dehydrogenase (SDH) complex due to germ-line mutations [1] or epigenetic silencing [17] has been shown to be oncogenic in paraganglioma/pheochromocytoma [18], gastrointestinal stromal tumors (GIST) [19, 20], renal…”
BackgroundPheochromocytoma: When to search a germline defect?
Buffet, A., Burnichon, N., Amar, L., & Gimenez‐Roqueplo, A. (2018) · La Presse Médicale · doi:10.1016/j.lpm.2018.07.003 · Cited by 14
Self-citationRoh, T. H., Yim, H., Roh, J., Lee, K. B., Park, S. H., Jeong, S., Kim, S.-H., & Kim, J.-H. (2019) · Scientific Reports · doi:10.1038/s41598-019-42338-z · Cited by 14
Pheochromocytoma/paraganglioma preclinical models: which to use and why?
Martinelli, S., Maggi, M., & Rapizzi, E. (2020) · Endocrine Connections · doi:10.1530/ec-20-0472 · Cited by 14
Model systems in SDHx-related pheochromocytoma/paraganglioma
Takács‐Vellai, K., Farkas, Z., Ősz, F., & Stewart, G. W. (2021) · Cancer and Metastasis Reviews · doi:10.1007/s10555-021-10009-z · Cited by 16
A critical role for heme synthesis and succinate in the regulation of pluripotent states transitions
Detraux, D., Caruso, M., Feller, L., Fransolet, M., Meurant, S., Mathieu, J., Arnould, T., & Renard, P. (2023) · eLife · doi:10.7554/elife.78546 · Cited by 14
“…we show here that the succinate accumulation outside mitochondria leads to a global reduction in cytosine demethylation activity of the TETs and histone demethylation as previously observed in cancers after accumulation of succinate or SDH mutations ( Letouzé et al., 2013 ; Xiao et al., 2012 ).”
Nambuba, J., Därr, R., Janssen, I., Bullova, P., Adams, K. T., Millo, C., Bourdeau, I., Kassai, A., Yang, C., Kebebew, E., et al. (2015) · AACE Clinical Case Reports · doi:10.4158/ep15759.cr · Cited by 14
Therapies targeting the signal pathways of pheochromocytoma and paraganglioma
Liu, Y., Liu, L., & Zhu, F. (2019) · OncoTargets and Therapy · doi:10.2147/ott.s219056 · Cited by 14
15 YEARS OF PARAGANGLIOMA: Metabolism and pheochromocytoma/paraganglioma
Mannelli, M., Rapizzi, E., Fucci, R., Canu, L., Ercolino, T., Luconi, M., & Young, W. F. (2015) · Endocrine Related Cancer · doi:10.1530/erc-15-0215 · Cited by 15
Animal and Cell Culture Models of PPGLs – Achievements and Limitations
Karna, B., Pellegata, N. S., & Mohr, H. (2024) · Hormone and Metabolic Research · doi:10.1055/a-2204-4549 · Cited by 15
“One example of such cell models is the imCC cells, de - rived from primary Sdhb knockout mouse adrenomedullary cells (non tumor cells), as described by Letouzé et al. (2013) [45].”
BackgroundMethodCrona, J., Ljungström, V., Welin, S., Walz, M. K., Hellman, P., & Björklund, P. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133210 · Cited by 13
Targeting the interplay between metabolism and epigenetics in cancer
Montellier, E., & Gaucher, J. (2018) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000501 · Cited by 13
Pheochromocytomes et paragangliomes pédiatriques: revue de la littérature
Garnier, S., Réguerre, Y., Orbach, D. H., Brugières, L., & Kalfa, N. (2014) · Bulletin du Cancer · doi:10.1684/bdc.2014.2031 · Cited by 13
Precision Surgery for Pheochromocytomas and Paragangliomas
Wiseman, D., Lakis, M. E., & Nilubol, N. (2019) · Hormone and Metabolic Research · doi:10.1055/a-0926-3618 · Cited by 13
“PNMT is the enzyme that converts norepinephrine to epinephrine.”
BackgroundInfluentialMetabolomics in the Diagnosis of Pheochromocytoma and Paraganglioma
Dwight, T., Kim, E., Novos, T., & Clifton-Bligh, R. J. (2019) · Hormone and Metabolic Research · doi:10.1055/a-0926-3790 · Cited by 14
Cedó, L., Madeira, A., & Caro, P. (2025) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2025.10.007 · Cited by 14
Mitochondrial metabolism in cancer stem cells (CSCs): molecular and diagnostic implications
Psvv, C., Sunil, S., Thuyyath, N., Kokkanti, R. R., & Lavudi, K. (2026) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2026.1741800 · Cited by 13
“Conversely, accumulation of succinate and fumarate, often observed in tumors with mutation in SDH or FH, inhibits these dioxygenases, leading to epigenetic dysregulation that favors stem-like programs (Sciacovelli et al., 2016; Letouzé et al., 2013).”
Somatic Mutation Profiling in Head and Neck Paragangliomas
Savvateeva, M. V., Kudryavtseva, A. V., Lukyanova, E., Kobelyatskaya, A. A., Pavlov, V., Fedorova, M., Pudova, E. A., Guvatova, Z. G., Kalinin, D. V., Golovyuk, A. L., et al. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac250 · Cited by 12
Preferential MGMT hypermethylation in SDH-deficient wild-type GIST
Giger, O., ten Hoopen, R., Shorthouse, D., Abdullahi, S., Bulusu, V. R., Jadhav, S., Maher, E. R., & Casey, R. T. (2022) · Journal of Clinical Pathology · doi:10.1136/jcp-2022-208462 · Cited by 12
Wang, K., Fischer, A., Macciò, U., Hantel, C., Beuschlein, F., Grossman, A. B., Pacák, K., & Nölting, S. (2024) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2024.101913 · Cited by 13
Mutation of the Cell Cycle Regulator p27kip1 Drives Pseudohypoxic Pheochromocytoma Development
Mohr, H., Ballke, S., Bechmann, N., Gulde, S., Malekzadeh‐Najafabadi, J., Peitzsch, M., Ntziachristos, V., Steiger, K., Wiedemann, T., & Pellegata, N. S. (2021) · Cancers · doi:10.3390/cancers13010126 · Cited by 12
“SDHx- and FH-mutated human p-PPGL lose the epigenetic marker 5-hmC and this associates with DNA hypermethylation [19].”
BackgroundInfluentialShifting the Gears of Metabolic Plasticity to Drive Cell State Transitions in Cancer
Wu, Z., Lee, Y. F., Yeo, X. H., Loo, S. Y., & Tam, W. L. (2021) · Cancers · doi:10.3390/cancers13061316 · Cited by 14
“Furthermore, mutations in SDHB have been linked to hypermethylation of promoter CpG islands that promote Snail and Slug activation, pointing to multiple mechanisms through which TCA cycle enzymes could epigenetically regulate the EMT program [76,77].”
Backgroundda Silva, I., Vieira, R. D. C., Stella, C., Loturco, E. G., Carvalho, A. L., Véo, C. A. R., Scapulatempo‐Neto, C., Silva, S. M., D’Amora, P., Salzgeber, M. B., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.25839 · Cited by 12
“These oncometabolites also enhance histone and DNA methylation [39, 40] leading to genome-wide epigenetic reprogramming [41].”
BackgroundBalnis, J., Tufts, A., Jackson, E. L., Drake, L. A., Singer, D. V., Lacomis, D., Lee, C. G., Elias, J. A., Doles, J. D., Maher, L. J., et al. (2024) · Science Advances · doi:10.1126/sciadv.ado8549 · Cited by 13
“In cancer cellular lines, SDHC KO has been shown to establish a repressive hypermethylated DNA landscape that contributes to the maintenance of the transformed phenotype ( 32 ).”
BackgroundThe interplay of metabolic and epigenetic players in disease development
Chakraborty, P., & Mukherjee, C. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.150621 · Cited by 11
Chen, H., Zhu, W., Li, X., Xue, L., Wang, Z., & Wu, H. (2017) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-017-2355-0 · Cited by 11
Al‐Obaidy, K. I., Alruwaii, Z. I., Williamson, S. R., & Liang Cheng, C. (2022) · Histopathology · doi:10.1111/his.14641 · Cited by 11
“The pathogenic role of SDH mutation in tumorigenesis is not fully understood; however, the accumulation of intracellular succinate is thought to be related to an oncogenic effect caused by PHD enzyme inhibition and genome-wide hypermethylation (Figure 2).(101,102) As such, there are no evidence-based treatment/guideli…”
BackgroundBaysal, B. E., Alahmari, A. A., Rodrick, T. C., Tabaczynski, D., Curtin, L. I., Seshadri, M., Jones, D. R., & Sexton, S. (2022) · JCI Insight · doi:10.1172/jci.insight.158737 · Cited by 12
“Increased succinate relative to oxoglutarate inhibits α-ketoglutarate–dependent enzymes, including HIF prolyl hydroxylases (68), Jumonji domain histone demethylases (69), and TET family of 5-methyldeoxycytosine hydroxylases (70), contributing to pseudohypoxia and hypermethylation in PGL tumors.”
BackgroundNDUFA4 promotes the progression of head and neck paraganglioma by inhibiting ferroptosis
Wang, Z., Tao, E., Chen, Y., Wang, Q., Liu, M., Wei, L., Xu, S., Chen, W., & Zhong, C. (2023) · Biochemistry and Cell Biology · doi:10.1139/bcb-2023-0018 · Cited by 11
DNA methylation analysis in malignant pheochromocytoma and paraganglioma
Oishi, T., Iino, K., Okawa, Y., Kakizawa, K., Matsunari, S., Yamashita, M., Taniguchi, T., Maekawa, M., Suda, T., & Oki, Y. (2016) · Journal of Clinical & Translational Endocrinology · doi:10.1016/j.jcte.2016.12.004 · Cited by 11
“There are several reports on the genome-wide methylation analysis of metastatic PCC/PGL. Letouzé et al. reported 191 genes that characterized in significant hypermethylation in their promoter CpG island and were downregulated in succinate dehydrogenase (SDH) B-mutated PCC/PGLs [19].”
BackgroundInfluentialPheochromocytoma/Paraganglioma: A Poster Child for Cancer Metabolism
Tevosian, S. G., & Ghayee, H. K. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01991 · Cited by 11
Master regulator analysis of paragangliomas carrying SDHx, VHL, or MAML3 genetic alterations
Smestad, J. A., & Maher, L. J., III (2019) · BMC Cancer · doi:10.1186/s12885-019-5813-z · Cited by 11
Metadata
- Authors
- Letouzé, E., Martinelli, C., Loriot, C., Burnichon, N., Abermil, N., Ottolenghi, C., Janin, M., Menara, M., Nguyen, A. T., Benit, P., Buffet, A., Marcaillou, C., Bertherat, J., Amar, L., Rustin, P., De Reyniès, A., Gimenez-Roqueplo, A.-P., & Favier, J.
- Affiliations
- Inserm (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Hôpital Necker-Enfants Malades (FR)
- IntegraGen (France) (FR)
- Corresponding author
- Favier, Judith
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 23
- Issue
- 6
- Pages
- 739-752
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2061662711
- Semantic Scholar
- 12ff63634482848e635a81bd0e943c6b9634ac9a
- Cited by
- 776
- References
- 60
- Citations by year
- 2026: 41 · 2025: 34 · 2024: 61 · 2023: 55 · 2022: 53 · 2021: 65 · 2020: 53 · 2019: 70 · 2018: 59 · 2017: 79 · 2016: 58 · 2015: 73 · 2014: 50 · 2013: 22
- FWCI
- 66.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agence Nationale de la Recherche
- Core Research for Evolutional Science and Technology
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Health Sciences › Medicine › Clinical Neurology › Neurofibromatosis and Schwannoma Cases
- Keywords
- paraganglioma, succinate dehydrogenase, SDHB mutation, DNA hypermethylation, succinate accumulation, epigenetic silencing, neuroendocrine differentiation, FH mutations, decitabine, chromaffin cells, TCA cycle, tumor malignancy
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Cell Movement, Child, Female, Glioblastoma, Histones, Humans, Male, Middle Aged, Paraganglioma, Phenotype, Pheochromocytoma, Succinate Dehydrogenase, Colorectal Neoplasms, DNA Methylation, Chromaffin Cells, Gene Silencing, Epigenesis, Genetic, Mice, Gene Knockout Techniques, Transcriptome
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