The DOI matches its Crossref record; 58 of the 60 references it cites were found in a registry or an index.
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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BackgroundUniversal Genetic Screening Uncovers a Novel Presentation of an SDHAF2 Mutation
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McEvoy, C. R. E., Koe, L., Choong, D., Leong, H. S., Xu, H., Karikios, D. J., Plew, J. D., Prall, O. W. J., FELLOWES, A. P., & Fox, S. B. (2018) · npj Precision Oncology · doi:10.1038/s41698-018-0053-2 · Cited by 39
“The mechanism of SDH-deficient tumorigenesis appears to involve the accumulation of succinate in the cytosol and its subsequent oncogenic effects caused by both hypoxia inducible factor (HIF)-α prolyl hydroxylase inhibition(1) and the induction of genome-wide hypermethylation due to TET enzyme inhibition.(2,3) SDH-def…”
BackgroundMetabolic Regulation of Epithelial to Mesenchymal Transition: Implications for Endocrine Cancer
Bhattacharya, D., & Scimè, A. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00773 · Cited by 39
Metabolism, Epigenetics, and Causal Inference in Heart Failure
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Significance of Alpha-inhibin Expression in Pheochromocytomas and Paragangliomas
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Metabolic Drivers in Hereditary Cancer Syndromes
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“…class aKGDDs, the DNA demethylases called ten-eleven translocation (TET) proteins (Hoekstra et al. 2015, Laukka et al. 2016, Xiao et al. 2012), leading to CpG (5′−C−phosphate−G−3′) island hypermethylation, a phenotype later termed CIMP (CpG island methylator phenotype) (Letouze et al. 2013).”
BackgroundInfluentialA xenograft and cell line model of SDH-deficient pheochromocytoma derived from Sdhb+/− rats
Powers, J. F., Cochran, B., Baleja, J., Sikes, H. D., Pattison, A., Zhang, X., Lomakin, I., Shepard-Barry, A., Pacák, K., Moon, S. J., et al. (2020) · Endocrine Related Cancer · doi:10.1530/erc-19-0474 · Cited by 39
“The presence of these markers indicates that they are not an irrelevant or dedifferentiated cell type, while the relatively low expression is comparable to that in human tumors (Letouze et al. 2013).”
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Moog, S., Lussey‐Lepoutre, C., & Favier, J. (2020) · Endocrine Related Cancer · doi:10.1530/erc-20-0346 · Cited by 42
Self-citationHeme Exporter FLVCR Is Required for T Cell Development and Peripheral Survival
Philip, M., Funkhouser, S. A., Chiu, E. Y., Phelps, S. R., Delrow, J. J., Cox, J. E., Fink, P. J., & Abkowitz, J. L. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402172 · Cited by 35
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“For instance, succinate accumulation in SDH-deficient tumors can silence tumor suppressor genes via hypermethylation [31], while fumarate accumulation in FH-deficient tumors has been linked to silencing of neuroendocrine differentiation genes [32].”
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“…are present in a tumor (Baysal et al. 2000, Astuti et al. 2003, 2004, Baysal 2003, 2004, 2008, Eng et al. 2003, Gimenez-Roqueplo et al. 2003, Ni et al. 2008, 2012, Sandgren et al. 2010, Bardella et al. 2011, Killian et al. 2013, Letouze et al. 2013) as the starting point for tumor development.”
Kľučková, K., Thakker, A., Vettore, L. A., Escribano-Gonzalez, C., Hindshaw, R. L., Tearle, J. L. E., Goncalves, J., Kaul, B., Lavery, G. G., Favier, J., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201901456r · Cited by 36
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“Furthermore, epigenetic and metabolomic profiling, immunohistochemistry (IHC) and in vivo functional imaging can all be applied to further subcharacterize PPGL (16).”
BackgroundGermline SUCLG2 Variants in Patients with Pheochromocytoma and Paraganglioma.
Vanova, K. H., Pang, Y., Krobova, L., Kraus, M., Nahacka, Z., Boukalová, Š., Pack, S., Zobalova, R., Zhu, J., Huynh, T., et al. (2021) · Journal of the National Cancer Institute · doi:10.1093/jnci/djab158 · Cited by 32
“These and other genetic, epigenetic, and relevant mechanistic studies on PPGL have increased our understanding of their pathogenesis and clinical behavior and uncovered potential new therapeutic targets in these hard-to-treat tumors (3,7,8).”
BackgroundCatecholamine Metabolism in Paraganglioma and Pheochromocytoma: Similar Tumors in Different Sites?
Grouzmann, E., Tschopp, O., Triponez, F., Matter, M., Bilz, S., Brändle, M., Tilman, D., Sigrist, S., Zulewski, H., Henzen, C., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125426 · Cited by 33
“VHL-related tumors that led to a downregulation of mRNA synthesis [22, 23].”
BackgroundOncometabolic Nuclear Reprogramming of Cancer Stemness
Menéndez, J. A., Corominas-Faja, B., Cuyàs, E., García, M. G., Fernández‐Arroyo, S., Fernández, A. F., Joven, J., Fraga, M. F., & Alarcón, T. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2015.12.012 · Cited by 34
“…rewiring of lineage-specific differentiation and in the promotion of stem cell-like transcriptional signatures (Chowdhury et al., 2011; Killian et al., 2013; Letouzé et al., 2013; Lu et al., 2012; Terunuma et al., 2014; Saha et al., 2014; Xiao et al., 2012; Xu et al., 2011; Yang et al., 2013).”
BackgroundZong, L., Abe, M., Ji, J., Zhu, W., & Yu, D. (2016) · Clinical and Translational Gastroenterology · doi:10.1038/ctg.2016.14 · Cited by 34
“In paragangliomas, Letouze et al.(41) reported that SDH mutation was a key factor in causing CIMP by interplaying between the Krebs cycle and 2-oxoglutaratedependent (2-OG) histone and DNA demethylases.”
BackgroundGladitz, J., Klink, B., & Seifert, M. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0544-y · Cited by 33
“Succinate accumulated in SDHB-mutated cells inhibits alpha-ketoglutaratedependent enzymes leading to the activation of hypoxia induced genes and hypermethylation of DNA and histones in paraganglioma [4, 40].”
Flynn, A., Pattison, A., Balachander, S., Boehm, E., Bowen, B., Dwight, T., Rossello, F. J., Hofmann, O., Martelotto, L. G., Zethoven, M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-57595-y · Cited by 37
“Succinate excess also inhibits other 2-oxoglutarate-dependent dioxygenases, including TET2 and jumonji histone lysine demethylases, causinggenome-widehypermethylationand epigenetic reprogramming 8,9 .”
HRAS mutation prevalence and associated expression patterns in pheochromocytoma
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Senescence-Inflammatory Regulation of Reparative Cellular Reprogramming in Aging and Cancer
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“…consequent accumulation of the histone demethylase (HDM) inhibitor succinate, which establishes a hypermethylator phenotype and the epigenetic silencing of key differentiation genes (Letouzé et al., 2013; Yang and Pollard, 2013), tend to present at a younger age (Lips et al., 2006; Chetty, 2010).”
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Garrigue, P., Bodin-Hullin, A., Balasse, L., Fernandez-Sauze, S., Essamet, W., Dignat‐George, F., Pacák, K., Guillet, B. A., & Taïeb, D. (2017) · Journal of Nuclear Medicine · doi:10.2967/jnumed.117.192674 · Cited by 33
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“In a small number of cases, mutations in other HIF-related genes have been reported including PHD2 [122,123], PHD1 [124], HIF2A [122,125,126], FH [127,128], and IDH1 [122].”
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Li, A. M., & Ye, J. (2023) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-062822-120857 · Cited by 31
Oxygen Concentration Controls Epigenetic Effects in Models of Familial Paraganglioma
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“Members of the TET family of 5-methylcytosine (5mdC) hydroxylases are also α-KG-dependent dioxgenases that are inhibited by succinate accumulation upon SDH loss [11,12,55].”
BackgroundMethodInfluentialGenetic and biochemical intricacy shapes mitochondrial cytopathies
Turnbull, D. M., & Rustin, P. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.02.003 · Cited by 32
Self-citationAdvances and challenges in understanding histone demethylase biology
Nowak, R. P., Tumber, A., Johansson, C., Che, K. H., Brennan, P. E., Owen, D. R., & Oppermann, U. C. T. (2016) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2016.06.021 · Cited by 32
“Furthermore, several genetic studies highlight mutations in enzymes of the tricarboxylic acid (TCA) cycle such as fumarate hydratase, succinate dehydrogenase or isocitrate dehydrogenase (IDH) as drivers of malignant transformation and progression [66, 67].”
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“SDH inactivation results in the accumulation of cellular succinate,[28] which acts as an important tumor‐promoting signaling molecule, an oncometabolite, in a plethora of cellular processes,[28] including metabolic epigenetic alterations,[29] promotion of proliferation,[30] and metastasis[11] in a diverse range of can…”
BackgroundRicci, L., Stanley, F. U., Eberhart, T., Mainini, F., Sumpton, D. P., & Cardaci, S. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-05927-5 · Cited by 34
“…activity and dysfunction of the TCA cycle in transformed cells, resulting in the consequent accumulation of succinate, an oncometabolite reprogramming gene expression in cancer by activating hypoxia-inducible factors and inhibiting α -ketoglutarate-dependent histone and DNA demethylases [17 – 19].”
Heiland, D. H., Gaebelein, A., Börries, M., Wörner, J., Pompe, N., Franco, P., Heynckes, S., Bartholomae, M., hAilín, D. Ó., Carro, M. S., et al. (2018) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-17-0680 · Cited by 34
Immunosurveillance encounters cancer metabolism
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“Certain cofactors for epigenetic modi fi ers, such as succinate and fumarate addressed above, can also trigger EMT (Colvin et al, 2016; Letouze et al, 2013; Sciacovelli et al, 2016; During cancer progression, tumor cells and tumor-in fi ltrating lymphocytes (TILs), including CD8 + T cells, regulatory…”
BackgroundCrona, J., Backman, S., Maharjan, R., Mayrhofer, M., Stalberg, P. L. H., Isaksson, A., Hellman, P., & Björklund, P. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2854 · Cited by 33
“In addition, SDHx tumors have been described to exhibit a hypermethylated signature (5, 9).”
BackgroundMetabolism – A cornerstone of cancer initiation, progression, immune evasion and treatment response
Lunt, S. Y., & Fendt, S. (2017) · Current Opinion in Systems Biology · doi:10.1016/j.coisb.2017.12.006 · Cited by 30
Pheochromocytomas and Paragangliomas: Bypassing Cellular Respiration
Cascón, A., Remacha, L., Calsina, B., & Robledo, M. (2019) · Cancers · doi:10.3390/cancers11050683 · Cited by 33
“In 2013, a germline mutation in FH was found in a patient with PCC by whole exome sequencing (WES) applied to a tumor displaying transcriptional and methylation (CIMP profile) similarities to SDH-mutant tumors [13].”
BackgroundInfluentialRole of succinate dehydrogenase deficiency and oncometabolites in gastrointestinal stromal tumors
Zhao, Y., Feng, F., Guo, Q., Wang, Y., & Zhao, R. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v26.i34.5074 · Cited by 35
Khatami, F., Amoli, M. M., & Tavangar, S. M. (2018) · Endocrine Regulations · doi:10.2478/enr-2018-0006 · Cited by 31
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The CIMP-high phenotype is associated with energy metabolism alterations in colon adenocarcinoma
Fedorova, M., Krasnov, G. S., Lukyanova, E., Zaretsky, A. R., Dmitriev, A. A., Melnikova, N. V., Moskalev, A., Kharitonov, S., Pudova, E. A., Guvatova, Z. G., et al. (2019) · BMC Medical Genetics · doi:10.1186/s12881-019-0771-5 · Cited by 31
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“Succinate also inhibits histone demethylases and its accumulation in SDH-deficient tissues results in genomic hypermethylation which has been shown in SDH-mutant paragangliomas [84].”
BackgroundSchweizer, L., Thierfelder, F., Thomas, C., Soschinski, P., Suwala, A. K., Stichel, D., Wefers, A. K., Wessels, L., Misch, M., Kim, H., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02218-7 · Cited by 30
“Tumors were shown to belong to three methylation subclusters (M1–M3) which are strongly associated with molecular subtypes: pseudohypoxic PGLs with genetic alterations in tricarboxylic acid cycle genes show DNA hypermethylation (TCGA M1 cluster), pseudohypoxic VHL- and EPAS1-related PGL show intermediate DNA methylati…”
BackgroundModels of parent-of-origin tumorigenesis in hereditary paraganglioma
Hoekstra, A. S., Devilee, P., & Bayley, J. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.05.011 · Cited by 30
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“dysregulation due to direct inhibition of histone lysine demethylases (KDM) and TET2, with consequent hypermethylation phenotypes and alteration of the expression of multiple genes involved in the control of cell proliferation and differentiation [59]; (ii) activation of succinate receptor (SUCNR1) with consequent act…”
BackgroundTargeting 2-oxoglutarate dehydrogenase for cancer treatment.
Chang, L., Chiang, S.-K., Chen, S., & Hung, M. (2022) · PubMed Central · Cited by 29
Cancer metastasis under the magnifying glass of epigenetics and epitranscriptomics
Janin, M., Dávalos, V., & Esteller, M. (2023) · Cancer and Metastasis Reviews · doi:10.1007/s10555-023-10120-3 · Cited by 30
“This inhibition of activity leads to a specific hypermethylation phenotype named CpG island methylator phenotype (CIMP), characterized by the concerted hypermethylation of a large number of genes that can drive tumor progression [163–165].”
BackgroundSelf-citation18F-DOPA: the versatile radiopharmaceutical
Taïeb, D., Impériale, A., & Pacák, K. (2016) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-016-3354-0 · Cited by 28
“It is now well established that these tumors exhibit tricarboxylic acid cycle (Krebs cycle) dysfunction with highly elevated accumulation of succinate [12] acting as an oncometabolite, deficiency in certain amino acids such as glutamate, aberration of catecholamine metabolism, a DNA hypermethylation phenotype [13], an…”
BackgroundUpdate on paragangliomas and pheochromocytomas
Lam, A. K.-Y. (2015) · Turkish Journal of Pathology · doi:10.5146/tjpath.2015.01318 · Cited by 28
Overcoming Radiation Resistance in Gliomas by Targeting Metabolism and DNA Repair Pathways
Meng, W., Palmer, J. D., Siedow, M. R., Haque, S. J., & Chakravarti, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042246 · Cited by 34
“The significant consequence of loss of SDH function is the accumulation of succinate, like neomorphic production of d-2HG in IDH1 mutant cancer, which causes the hypermethylation of DNA and histone 3 [46,47].”
BackgroundGenomic and Metabolic Hallmarks of SDH- and FH-deficient Renal Cell Carcinomas
Yoo, A., Tang, C., Zucker, M. R., Fitzgerald, K. N., DiNatale, R. G., Rappold, P. M., Weiss, K. L., Freeman, B., Lee, C., Schultz, N. D., et al. (2022) · European Urology Focus · doi:10.1016/j.euf.2021.12.002 · Cited by 29
“Both fumarate and succinate can act as potent inhibitors of α-ketoglutarate-dependent dioxygenases including DNA demethylases [6], and both have been implicated as drivers of hypermethylation phenotypes seen in RCC, paragangliomas, and pheochromocytomas [7,8], suggesting that loss of either of the two enzymes may conv…”
BackgroundPheochromocytoma: Gasping for Air
Jochmanová, I., Zhuang, Z., & Pacák, K. (2015) · Hormones and Cancer · doi:10.1007/s12672-015-0231-4 · Cited by 30
Establishment of a DNA methylation marker to evaluate cancer cell fraction in gastric cancer
Zong, L., Hattori, N., Yoda, Y., Yamashita, S., Takeshima, H., Takahashi, T., Maeda, M., Katai, H., Nanjo, S., Ando, T., et al. (2015) · Gastric Cancer · doi:10.1007/s10120-015-0475-2 · Cited by 28
“Extensive genomic and epigenomic analyses of a variety of human cancers, including gastric cancers (GCs), have been and are being conducted [1–4].”
BackgroundParagangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib
Verginelli, F., Perconti, S., Vespa, S., Schiavi, F., Prasad, S. C., Lanuti, P., Cama, A., Tramontana, L., Esposito, D. L., Guarnieri, S., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-017-1799-2 · Cited by 28
“AIF analyses confirmed that PGL cells of vascular and neural lineage always coexpressed immature markers associated with mesenchymal stem cells (CD44, vimentin) [14, 74, 75], the hypoxia-ZEB1 axis (HIF2A, ZEB1, NOTCH1, DLK1) [33, 37, 41, 42, 59, 70, 77], glucose uptake (GLUT4) [59] and vasculoneurogenesis (NOTCH1, DLK…”
BackgroundThe role of tumor metabolism in modulating T-Cell activity and in optimizing immunotherapy
Ganjoo, S., Gupta, P., Corbali, H. I., Nanez, S., Riad, T. S., Duong, L. K., Barsoumian, H. B., Masrorpour, F., Jiang, H., Welsh, J. W., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1172931 · Cited by 32
Novel insight into the Warburg effect: Sweet temptation
Zhang, H., Liu, S., Fu, S., Zhao, Q., Wang, Y., Yuan, Y., & Zhang, C. (2025) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2025.104844 · Cited by 33
ATRX driver mutation in a composite malignant pheochromocytoma
Comino‐Méndez, I., Tejera, Á. M., Currás-Freixes, M., Remacha, L., Gonzálvo, P., Tonda, R., Letón, R., Blasco, M. A., Robledo, M., & Cascón, A. (2016) · Cancer Genetics · doi:10.1016/j.cancergen.2016.04.058 · Cited by 29
Lameirinhas, A., Miranda‐Gonçalves, V., Henrique, R., & Jerónimo, C. (2019) · Genes · doi:10.3390/genes10040264 · Cited by 28
“Sciacovelli et al. demonstrated that intracellular fumarate accumulation drives changes in EMT genes, such as zinc finger E-box binding homeobox (ZEB), snail family transcriptional repressor 1 (SNAI1) and vimentin (VIM), through inhibition of TETs and consequent anti-metastatic microRNA cluster downregulation, in muri…”
BackgroundNutritional Epigenetics in Cancer
Barrero, M. J., Cejas, P., Long, H. W., & de Molina, A. R. (2022) · Advances in Nutrition · doi:10.1093/advances/nmac039 · Cited by 27
Folguera-Blasco, N., Cuyàs, E., Menéndez, J. A., & Alarcón, T. (2018) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1006052 · Cited by 26
Kaławaj, K., Sławińska-Brych, A., Mizerska-Kowalska, M., Żurek, A., Bojarska-Junak, A. A., Kandefer‐Szerszeń, M., & Zdzisińska, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249406 · Cited by 27
Karlsson, J., Valind, A., Jansson, C., O’Sullivan, M. J., Mengelbier, L. H., & Gisselsson, D. (2016) · Oncotarget · doi:10.18632/oncotarget.7152 · Cited by 26
“It is well established that an aberrant hypermethylation of tumor DNA can be caused by mutations in epigenetic modifiers such as IDH1, IDH2 , TET1, TET2 , and SDH -subunits [18, 19].”
Yamazaki, Y., Gao, X., Pecori, A., Nakamura, Y., Tezuka, Y., Omata, K., Ono, Y., Morimoto, R., Satoh, F., & Sasano, H. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.587769 · Cited by 30
Succinate dehydrogenase and MYC-associated factor X mutations in pituitary neuroendocrine tumours
Loughrey, P. B., Roncaroli, F., Healy, E. G., Weir, P., Madhu, B., Casey, R. T., Hunter, S. J., & Korbonits, M. (2022) · Endocrine Related Cancer · doi:10.1530/erc-22-0157 · Cited by 28
The Immune Landscape of Pheochromocytoma and Paraganglioma: Current Advances and Perspectives
Uher, O., Vanova, K. H., Taïeb, D., Calsina, B., Robledo, M., Clifton-Bligh, R. J., & Pacák, K. (2024) · Endocrine Reviews · doi:10.1210/endrev/bnae005 · Cited by 31
Féral, C. C., Tissot, F. S., Tosello, L., Fakhry, N., Sebag, F. A., Pacák, K., & Taïeb, D. (2016) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-016-3586-z · Cited by 26
“Based on recent work, a possibility could imply that certain SDHx tumors display epigenetic regulation that reduces the activity or expression of LAT [26].”
BackgroundMitochondrial Deficiencies in the Predisposition to Paraganglioma
Lussey‐Lepoutre, C., Buffet, A., Gimenez‐Roqueplo, A., & Favier, J. (2017) · Metabolites · doi:10.3390/metabo7020017 · Cited by 28
“Although no study is yet available in humans, some promising results are now starting to bear fruit from in vitro studies, suggesting that drugs targeting epigenetic pathways might constitute useful alternative treatments for SDHx-related or FH-related malignant PPGLs in the future [43].”
BackgroundInfluentialSelf-citationThe Emerging Role of Succinate Dehyrogenase Genes (SDHx) in Tumorigenesis
Nazar, E., Khatami, F., Saffar, H., & Tavangar, S. M. (2019) · International Journal of Hematology-Oncology and Stem Cell Research · doi:10.18502/ijhoscr.v13i2.692 · Cited by 26
Activating FGFR1 Mutations in Sporadic Pheochromocytomas
Welander, J., Łysiak, M., Brauckhoff, M., Brunaud, L., Söderkvist, P., & Gimm, O. (2017) · World Journal of Surgery · doi:10.1007/s00268-017-4320-0 · Cited by 26
Cancer and the Kidney: The Growth of Onco-nephrology
Perazella, M. A., Berns, J. S., & Rosner, M. H. (2013) · Advances in Chronic Kidney Disease · doi:10.1053/j.ackd.2013.09.002 · Cited by 26
Tejero, J. D., Hesterberg, R. S., Drápela, S., Ilter, D., Raizada, D., Lazure, F., Kashfi, H., Liu, M., Silvane, L., Avram, D., et al. (2024) · Oncogene · doi:10.1038/s41388-024-03191-1 · Cited by 26
“Increased succinate levels have been shown to cause signi fi cant changes in epigenetic regulation, thereby dictating cell fate [38, 39].”
Monteagudo, M., Martínez, P., Leandro-Garcia, L. J., Martínez‐Montes, Á. M., Calsina, B., Pulgarín-Alfaro, M., Díaz‐Talavera, A., Mellid, S., Letón, R., Gil, E., et al. (2021) · Cancers · doi:10.3390/cancers13194758 · Cited by 23
Tumour microenvironment in pheochromocytoma and paraganglioma
Martinelli, S., Amore, F., Canu, L., Maggi, M., & Rapizzi, E. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1137456 · Cited by 26
“Regarding human Pheo/PGLs, transcriptome and methylome data revealed that high levels of promoter methylation of of Keratin19 (KRT19) were able to distinguish SDHB-mutated tumours from all other Pheo/PGL tumours (96, 97).”
BackgroundEpigenetics of pheochromocytoma and paraganglioma
Björklund, P., & Backman, S. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.06.016 · Cited by 25
Analysis of SDHAF3 in familial and sporadic pheochromocytoma and paraganglioma
Dwight, T., Na, U., Kim, E., Zhu, Y., Richardson, A. L., Robinson, B. G., Tucker, K., Gill, A. J., Benn, D. E., Clifton-Bligh, R. J., et al. (2017) · BMC Cancer · doi:10.1186/s12885-017-3486-z · Cited by 25
Evenepoel, L., van Nederveen, F. H., Oudijk, L., Papathomas, T. G., Restuccia, D. F., Belt, E. J. T., de Herder, W. W., Feelders, R. A., Franssen, G. J. H., Hamoir, M., et al. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01314 · Cited by 24
Yates, J., & Boeva, V. (2022) · Briefings in Bioinformatics · doi:10.1093/bib/bbab610 · Cited by 24
“ABAC: adjusted balanced accuracy; ACC: adrenocortical carcinoma; BLCA: Bladder Urothelial Carcinoma; BRCA: breast invasive carcinoma; CESC: cervical squamous cell carcinoma and endocervical adenocarcinoma; CI: confidence interval; CGI: CpG Island; CIMP: CpG island methylator phenotype; COAD: colon adenocarcinoma; DAVI…”
InfluentialBackman, S., Maharjan, R., Falk-Delgado, A., Crona, J., Cupisti, K., Stalberg, P. L. H., Hellman, P., & Björklund, P. (2017) · Scientific Reports · doi:10.1038/srep44943 · Cited by 23
Lee, C., Gundem, G., Lee, W., Chen, Y., Cross, J. R., Dong, Y., Redzematovic, A., Mano, R., Wei, E. Y., Cheng, E. H. Y., et al. (2017) · JCO Precision Oncology · doi:10.1200/po.16.00007 · Cited by 24
“These studies highlighted the role of accumulated succinate as an oncometabolite that inhibits a-ketoglutarate–dependent dioxygenases, resulting in metabolic and epigenetic changes.(60-63) In fact, our genomic study of these patients demonstrated that the complete loss ofSDHBconstitutes the first event in the pathogen…”
BackgroundMethodNew insights on the pathogenesis of paraganglioma and pheochromocytoma
Kantorovich, V., & Pacák, K. (2018) · F1000Research · doi:10.12688/f1000research.14568.1 · Cited by 24
Casey, R. T., ten Hoopen, R., Ochoa, E., Challis, B., Whitworth, J., Smith, P., Martín, J., Clark, G. R., Rodger, F., Maranian, M. J., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-46124-9 · Cited by 24
Emerging role of dopamine in neovascularization of pheochromocytoma and paraganglioma
Osinga, T. E., Links, T. P., Dullaart, R. P. F., Pacák, K., van der Horst‐Schrivers, A. N. A., Kerstens, M. N., & Kema, I. P. (2017) · The FASEB Journal · doi:10.1096/fj.201601131r · Cited by 28
“The increased succinate concentrations in SDHx-related PCC and PGL may cause DNA hypermethylation of the gene encoding the DA D2 receptor through inhibition of the histone lysine demethylases (KDMs) and the ten-eleven translocation (TET) enzymes, as has been shown in SDH-knockout mice (137, 138).”
BackgroundMethodTargeting Mitochondrial Oncometabolites: A New Approach to Overcome Drug Resistance in Cancer
Godel, M., Ortone, G., Anobile, D. P., Pasino, M., Randazzo, G., Riganti, C., & Kopecka, J. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13050762 · Cited by 23
Metabolic dependencies of metastasis-initiating cells in female breast cancer
Young, C. M., Beziaud, L., Dessen, P., Alonso, A. M., Santamaria‐Martínez, A., & Huelsken, J. (2023) · Nature Communications · doi:10.1038/s41467-023-42748-8 · Cited by 26
“Other TCA cycle metabolites have been shown to regulate histone methylation of EMT genes, such as succinate 44 and fumarate 45 .”
The role of mutation of metabolism-related genes in genomic hypermethylation
Waterfall, J. J., Killian, J. K., & Meltzer, P. S. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.08.003 · Cited by 23
Genetically Modeled Mice with Mutations in Mitochondrial Metabolic Enzymes for the Study of Cancer
Piruat, J. I., & Millán‐Uclés, Á. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00200 · Cited by 21
“Another conditional “floxed” Sdh-mutant has been reported for the SdhB subunit (7).”
BackgroundHasumi, H., & Yao, M. (2018) · Cancer Science · doi:10.1111/cas.13503 · Cited by 24
“Alteration of SDH leads to the metabolic shift towards glycolysis as well as to the accumulation of succinate, which drives tumor progression in the same way as does the accumulation of fumarate in FH-deficient kidney cells.(38,39)”
BackgroundMetformin targets histone acetylation in cancer-prone epithelial cells
Cuyàs, E., Fernández‐Arroyo, S., Joven, J., & Menéndez, J. A. (2016) · Cell Cycle · doi:10.1080/15384101.2016.1249547 · Cited by 23
SDH defective cancers: molecular mechanisms and treatment strategies
Wang, J., Yuan, T., Yang, B. W., He, Q., & Zhu, H. (2025) · Cell Biology and Toxicology · doi:10.1007/s10565-025-10022-w · Cited by 24
Advances in paraganglioma–pheochromocytoma cell lines and xenografts
Bayley, J., & Devilee, P. (2020) · Endocrine Related Cancer · doi:10.1530/erc-19-0434 · Cited by 24
Fuchs, T. L., Luxford, C., Clarkson, A., Sheen, A., Sioson, L., Elston, M. S., CROXSON, M. S., Dwight, T., Benn, D. E., Tacon, L. J., et al. (2022) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000001945 · Cited by 22
Mitochondrial carriers in inflammation induced by bacterial endotoxin and cytokines
Iacobazzi, V., Infantino, V., Castegna, A., Menga, A., Palmieri, E. M., Convertini, P., & Palmieri, F. (2016) · Biological Chemistry · doi:10.1515/hsz-2016-0260 · Cited by 21
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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