ArticleEndocrine-related cancer2015
Germline and somatic SDHx alterations in apparently sporadic differentiated thyroid cancer.
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Article in Endocrine-related cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21citing papers in PubMed
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21 citing papers in PubMed, 39 citations in OpenAlex.
- Article
- Familial Clinical Heterogeneity of Medullary Thyroid Cancer with GermlineJournal of clinical research in pediatric endocrinology · 2025Article
- Mitochondrial Metabolomics in Cancer: Mass Spectrometry-Based Approaches for Metabolic Rewiring Analysis and Therapeutic Discovery.Metabolites · 2025Review
- SDH defective cancers: molecular mechanisms and treatment strategies.Cell biology and toxicology · 2025Review
- Reprogramming of Thyroid Cancer Metabolism: from Mechanism to Therapeutic Strategy.Molecular cancer · 2025Review
- Tumor promoting effect of PDLIM2 downregulation involves mitochondrial ROS, oncometabolite accumulations and HIF-1α activation.Journal of experimental & clinical cancer research : CR · 2024Article
- Targeting mitochondrial metabolism for precision medicine in cancer.Cell death and differentiation · 2022Review
- Model systems in SDHx-related pheochromocytoma/paraganglioma.Cancer metastasis reviews · 2021Review
- Non-medullary Thyroid Cancer Susceptibility Genes: Evidence and Disease Spectrum.Annals of surgical oncology · 2021Article
- Metabolic adaptation in hypoxia and cancer.Cancer letters · 2021Review
- Role of succinylation modification in thyroid cancer and breast cancer.American journal of cancer research · 2021Review
- Rescue of TCA Cycle Dysfunction for Cancer Therapy.Journal of clinical medicine · 2019Review
- A Family With a Carotid Body Paraganglioma and Thyroid Neoplasias With a NewJournal of the Endocrine Society · 2019Article
- The loss of succinate dehydrogenase B expression is frequently identified in hemangioblastoma of the central nervous system.Scientific reports · 2019Article
- The Role of Immunohistochemistry and Molecular Analysis of Succinate Dehydrogenase in the Diagnosis of Endocrine and Non-Endocrine Tumors and Related Syndromes.Endocrine pathology · 2019Review
- Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genesJournal of medical genetics · 2018Article
- Chromatin Succinylation Correlates with Active Gene Expression and Is Perturbed by Defective TCA Cycle Metabolism.iScience · 2018Article
- Article
- Cowden syndrome-associated germline succinate dehydrogenase complex subunit D (SDHD) variants cause PTEN-mediated down-regulation of autophagy in thyroid cancer cells.Human molecular genetics · 2017Article
- Familiar Papillary Thyroid Carcinoma in a Large Brazilian Family Is Not Associated with Succinate Dehydrogenase Defects.European thyroid journal · 2016Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Ying NiGenomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA Genomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA Genomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA.
Spencer SeballosGenomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA.
Shireen GanapathiGenomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA.
Danielle GurinGenomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA.
Benjamin FletcherGenomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA.
Joanne NgeowGenomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA Genomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA.
Rebecca NagyGenomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA Genomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA.
Richard T KloosGenomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA Genomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA.
Matthew D RingelGenomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA Genomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA.
Thomas LaFramboiseGenomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA Genomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA Genomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA.
Charis EngGenomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA Genomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA Genomic Medicine InstituteLerner Research InstituteTaussig Cancer InstituteStanley Shalom Zielony Nursing InstituteCleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, Ohio 44195, USADivision of Medical OncologyNational Cancer Center, Singapore 169610, SingaporeDivisions of Human GeneticsEndocrinology and MetabolismDepartment of MedicineComprehensive Cancer CenterArthur G. James Cancer Hospital and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, USADepartments of Genetics and Genome SciencesEpidemiology and BiostatisticsCASE Comprehensive Cancer CenterCase Western Reserve University, Cleveland, Ohio 44116, USA Genomic Medicine Ins
The Ohio State University · USThe Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · US
Funding
Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3MSelective Modulation of Thyroidal RadioiodineP01CA124570 · NCI · OHIO STATE UNIVERSITY · PI RINGEL, MATTHEW D · 2008 to 2017
$23.4MTRAINING IN COMPUTATIONAL GENOMIC EPIDEMIOLOGY OF CANCERR25CA094186 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI LI, LI · 2002 to 2016
$6.8MNCI NIH HHS P01 CA124570NCI NIH HHS P01CA124570NCI NIH HHS P30 CA016058NCI NIH HHS R25 CA094186PHS HHS R25TCA094186
Abstract
Along with breast and endometrial cancers, thyroid cancer is a major component cancer in Cowden syndrome (CS). Germline variants in SDHB/C/D (SDHx) genes account for subsets of CS/CS-like cases, conferring a higher risk of breast and thyroid cancers over those with only germline PTEN mutations. To investigate whether SDHx alterations at both germline and somatic levels occur in apparently sporadic breast cancer and differentiated thyroid cancer (DTC), we analyzed SDHx genes in the following four groups: i) 48 individuals with sporadic invasive breast adenocarcinoma for germline mutation; ii) 48 (expanded to 241) DTC for germline mutation; iii) 37 pairs DTC tumor-normal tissues for germline and somatic mutation and mRNA expression levels; and iv) data from 476 patients in the Cancer Genome Atlas thyroid carcinoma dataset for validation. No germline SDHx variant was found in a pilot series of 48 breast cancer cases. As germline SDHx variants were found in our pilot of 48 thyroid cancer cases, we expanded to three series of DTC comprising a total 754 cases, and found 48 (6%) with germline SDHx variants (P<0.001 compared with 0/350 controls). In 513 tumors, we found 27 (5%) with large somatic duplications within chromosome 1 encompassing SDHC. Both papillary and follicular thyroid tumors showed consistent loss of SDHC/D gene expression (P<0.001), which is associated with earlier disease onset and higher pathological-TNM stage. Therefore, we conclude that both germline and somatic SDHx mutations/variants occur in sporadic DTC but are very rare in sporadic breast cancer, and overall loss of SDHx gene expression is a signature of DTC.
Indexed as
Adenocarcinoma, FollicularAdultAgedAged, 80 and overBreast NeoplasmsCarcinomaCarcinoma, Ductal, BreastCarcinoma, PapillaryFemaleGenetic VariationHumansMembrane ProteinsMiddle AgedMutationSuccinate DehydrogenaseThyroid Cancer, PapillaryMembrane ProteinsSDHB protein, humanSDHC protein, humanSDHD protein, humanSuccinate Dehydrogenasegene expressionpapillary thyroid cancerSDHxvariant
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