ArticleNeoplasia (New York, N.Y.)2015
Metabolome profiling by HRMAS NMR spectroscopy of pheochromocytomas and paragangliomas detects SDH deficiency: clinical and pathophysiological implications.
Article in Neoplasia (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 66 citations in OpenAlex.
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- Imaging of Pheochromocytomas and Paragangliomas.Endocrine reviews · 2024Review
- Toward Systems-Level Metabolic Analysis in Endocrine Disorders and Cancer.Endocrinology and metabolism (Seoul, Korea) · 2023Review
- Active Estrogen-Succinate Metabolism Promotes Heme Accumulation and Increases the Proliferative and Invasive Potential of Endometrial Cancer Cells.Biomolecules · 2023Article
- Metabolomics in paraganglioma: applications and perspectives from genetics to therapy.Endocrine-related cancer · 2023Article
- SDHx mutation and pituitary adenoma: can in vivo 1H-MR spectroscopy unravel the link?Endocrine-related cancer · 2023Article
- Performance comparison of three scaling algorithms in NMR-based metabolomics analysis.Open life sciences · 2023Article
- Succinate dehydrogenase and MYC-associated factor X mutations in pituitary neuroendocrine tumours.Endocrine-related cancer · 2022Review
- The Role of the Metabolome and Non-Coding RNA on Pheochromocytomas and Paragangliomas: An Update.Metabolites · 2022Article
- High throughput proteomic and metabolic profiling identified target correction of metabolic abnormalities as a novel therapeutic approach in head and neck paraganglioma.Translational oncology · 2021Article
- Loss of SDHB Promotes Dysregulated Iron Homeostasis, Oxidative Stress, and Sensitivity to Ascorbate.Cancer research · 2021Article
- From Metabolism to Genetics and Vice Versa: The Rising Role of Oncometabolites in Cancer Development and Therapy.International journal of molecular sciences · 2021Review
- Pheochromocytoma/paraganglioma: recent updates in genetics, biochemistry, immunohistochemistry, metabolomics, imaging and therapeutic options.Gland surgery · 2020Review
- Clinical implications of the oncometabolite succinate in SDHx-mutation carriers.Clinical genetics · 2020Review
- Metabolomics of Small Intestine Neuroendocrine Tumors and Related Hepatic Metastases.Metabolites · 2019Article
- Metabolomic prostate cancer fields in HRMAS MRS-profiled histologically benign tissue vary with cancer status and distance from cancer.NMR in biomedicine · 2019Article
- A metabolic database for biomedical studies of biopsy specimens by high-resolution magic angle spinning nuclear MR: a qualitative and quantitative tool.Magnetic resonance in medicine · 2019Article
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
Succinate dehydrogenase gene (SDHx) mutations increase susceptibility to develop pheochromocytomas/paragangliomas (PHEOs/PGLs). In the present study, we evaluate the performance and clinical applications of (1)H high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy-based global metabolomic profiling in a large series of PHEOs/PGLs of different genetic backgrounds. Eighty-seven PHEOs/PGLs (48 sporadic/23 SDHx/7 von Hippel-Lindau/5 REarranged during Transfection/3 neurofibromatosis type 1/1 hypoxia-inducible factor 2α), one SDHD variant of unknown significance, and two Carney triad (CTr)-related tumors were analyzed by HRMAS-NMR spectroscopy. Compared to sporadic, SDHx-related PHEOs/PGLs exhibit a specific metabolic signature characterized by increased levels of succinate (P < .0001), methionine (P = .002), glutamine (P = .002), and myoinositol (P < .0007) and decreased levels of glutamate (P < .0007), regardless of their location and catecholamine levels. Uniquely, ATP/ascorbate/glutathione was found to be associated with the secretory phenotype of PHEOs/PGLs, regardless of their genotype (P < .0007). The use of succinate as a single screening test retained excellent accuracy in distinguishing SDHx versus non-SDHx-related tumors (sensitivity/specificity: 100/100%). Moreover, the quantification of succinate could be considered a diagnostic alternative for assessing SDHx-related mutations of unknown pathogenicity. We were also able, for the first time, to uncover an SDH-like pattern in the two CTr-related PGLs. The present study demonstrates that HRMAS-NMR provides important information for SDHx-related PHEO/PGL characterization. Besides the high succinate-low glutamate hallmark, SDHx tumors also exhibit high values of methionine, a finding consistent with the hypermethylation pattern of these tumors. We also found important levels of glutamine, suggesting that glutamine metabolism might be involved in the pathogenesis of SDHx-related PHEOs/PGLs.
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