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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In the citing paper
“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
Citations
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications
Krueger, F., & Andrews, S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr167 · Cited by 5,275
Jones, P. A., & Baylin, S. B. (2007) · Cell · doi:10.1016/j.cell.2007.01.029 · Cited by 4,515
Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate
Ward, P. S., & Thompson, C. B. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.014 · Cited by 3,233
Xu, W., Yang, H., Liu, Y., Yang, Y., Wang, P., Kim, S.-H., Ito, S., Yang, C., Wang, P., Xiao, M.-T., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.12.014 · Cited by 2,875
CpG island methylator phenotype in colorectal cancer
Toyota, M., Ahuja, N., Ohe-Toyota, M., Herman, J. G., Baylin, S. B., & Issa, J. J. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.15.8681 · Cited by 2,562
Hypomethylation distinguishes genes of some human cancers from their normal counterparts
Feinberg, A. P., & Vogelstein, B. (1983) · Nature · doi:10.1038/301089a0 · Cited by 2,430
Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma
Noushmehr, H., Weisenberger, D. J., Diefes, K., Phillips, H. S., Pujara, K., Berman, B. P., Pan, F., Pelloski, C. E., Sulman, E. P., Bhat, K. P., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.03.017 · Cited by 2,337
Linking DNA methylation and histone modification: patterns and paradigms
Cedar, H., & Bergman, Y. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2540 · Cited by 2,267 · cited 1×
“As both H3K9 and H3K27 methylation are closely linked with DNA methylation (Cedar and Bergman, 2009), these effects on histone methylation may contribute to the establishment of the hypermethylator phenotype.”
BackgroundMonti, S., Tamayo, P., Mesirov, J., & Golub, T. (2003) · Machine Learning · doi:10.1023/a:1023949509487 · Cited by 2,116
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2 of the 60 references couldn’t be matched to a known paper.
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Items 801–813 of 813
Pearce, T. M., Cimino, P. J., Lucas, C.-H. G., Marker, D. F., Kulich, S. M., Skaugen, J. M., Kofler, J. K., Cho, B. B., Kurek, K., Conway, K. S., et al. (2026) · Acta Neuropathologica · doi:10.1007/s00401-026-03070-x
“…5 ′ UTR, 1st exon) with β > 0.30, and compared SELN against non-neoplastic regional controls (cerebral cortex, cerebellum, adenohypophysis, hypothalamus) and [42, 55, 74], rather than the CGI hypermethylation set against global/repetitive-element hypomethylation seen in most cancer methylomes [17].”
InfluentialMitochondrial Complex II in the regulation of immunopathology
Yamamoto, A., Sumii, Y., & Reddy, P. (2026) · Trends in Immunology · doi:10.1016/j.it.2026.07.013
Lim, E. S., Bayley, J., Gimenez‐Roqueplo, A., Clifton-Bligh, R. J., & Richter, S. (2026) · Endocrine Related Cancer · doi:10.1530/erc-26-0282
“…predominantly mediated by inhibition of α-ketoglutarate-dependent enzymes, such as prolyl hydroxylases that regulate hypoxia-inducible factor (HIF) stability, and of DNA and histone demethylases, resulting in pseudohypoxic signalling and epigenetic reprogramming, respectively (18, 19).”
Self-citationMolecular clusters and precision medicine in pheochromocytomas and paragangliomas
Almeida, M. Q., Dahia, P. L. M., & Robledo, M. (2026) · Endocrine Related Cancer · doi:10.1530/erc-26-0258
Metabolic context and cellular ploidy enable functional classification of SDHB exon3 variantsPreprint
Lewis, N., Richter, A., Cruz-García, A., Fritz‐Wallace, K., Gebhardt, M., Tippmann, F., William, D., Schröck, E., Duc, D. L., Richter, S., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-10666421/v1
Lorenzo, G. D., Kharrat, F., Hollan, F., Capaci, V., Balasan, N., Aloisio, M., Caponnetto, F., Beltrami, A. P., Romano, F., Ricci, G., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27177703
“The convergence of both proteomics and metabolomics indicates that there is coordinated metabolic regulation in EC-derived EVs, involving energy metabolism, redox homeostasis, and biosynthesis [31].”
Kandukuri, S. R., Lobo, A., Tsai, H., Aron, M., Jha, S., Hirsch, M. S., & Mohanty, S. (2026) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000002611
Lee, J., Hur, J., & Choi, H. (2026) · Journal of Medicinal Food · doi:10.1177/1096620x261481638
Cole, Y., Abramovich, I., Fernández-García, J., Docquier, F., MacFarlane, J., Xu, X., Andrésson, Þ., Indig, I. H., Wang, H., Krishnan, A. Y., et al. (2026) · Endocrine Related Cancer · doi:10.1530/erc-26-0323
“Even when oxygen levels are sufficient, SDHx -deficient cancer cells upregulate hypoxia pathways, termed pseudohypoxia, leading to both metabolic and epigenetic rewiring (3, 4).”
Noyer, L., Wang, L., Jishage, M., McDermott, M., Pezacki, A. T., Tao, A. Y., Ramasamy, R., Stadtfeld, M., Chang, C. J., & Feske, S. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.22.747582
Kopinski, P. K., Magi, I. J., & Dalvin, L. A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-19001-8.00026-x
Fan, Y., Zhang, H., Meng, S., Li, S., Lou, L., Xie, K., & Xie, J. (2026) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2026.10.022
Charting the Genetic Landscape and Clonal Architectures of Pheochromocytoma
Crona, J. (2014) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
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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