Forty percent of paragangliomas are linked to genetic syndromes, most commonly due to mutations of the succinate dehydrogenase (SDH) enzyme complex and are collectively known as paraganglioma syndromes, of which five are described.
In this study, we investigated mutations of SDH genes in six HPPS patients from four Japanese pedigrees using peripheral blood lymphocytes (from one patient with pheochromocytoma and five patients with neck paraganglioma) and tumor tissues (from two patients with paraganglioma).
SDH status should be considered for all patients with paraganglioma as it may be important for patients' lifelong follow-up as well as for familial considerations.
Mutations in mitochondrial complex II (succinate dehydrogenase; SDH) genes predispose to paraganglioma tumors that show constitutive activation of hypoxia responses.
Though most paragangliomas arise as sporadic tumors, the recent advantages in the genetic screening revealed that about 30 % of paragangliomas are linked to hereditary mutations, such as those involving SDH genes.
Transcriptional profiling analysis classified the tumor within cluster 2 of PCCs/PGLs (without SDH gene mutations) and identified downregulation of genes involved in neuronal development and homeostasis (NLGN4, CD99 and CSF2RA) as well as upregulation of Drosha, an important gene involved in miRNA and rRNA processing.
Mutations of the SDH gene are associated with many tumors, such as renal cell carcinoma, wild type gastrointestinal stromal tumors (WT GISTs) and hereditary paragangliomas/pheochromocytomas.
Targeted purine analysis in PGLs showed low adenine in cluster 1 compared with cluster 2 tumors (SDH P < .0001; VHL P < .05) whereas lower levels (P < .05) of guanosine and hypoxanthine were observed in RET tumors compared with SDH tumors.
We summarize the pathophysiological, clinical, laboratory, and morphological and functional imaging characteristics of SDH gene mutation PGLs, emphasizing F-FDG and F-DOPA PET/CT.
The aim of this study was to investigate interobserver variability among seven expert endocrine pathologists using a web-based virtual microscopy approach in a large multicenter pheochromocytoma/paraganglioma cohort (n=351): (1) 73 SDH mutated, (2) 105 non-SDH mutated, (3) 128 samples without identified SDH-x mutations, and (4) 45 with incomplete SDH molecular genetic analysis.
We suggest that F-FDG PET should be done in all patients with PGL due to SDH-B mutations, as it may show additional unsuspected lesions that may be missed by other tracers.
IDH1 and IDH2 mutations are found in many neoplasms, and germline alterations in SDH genes and FH predispose to pheochromocytoma/paraganglioma and other cancers.
Metabolome profiling by HRMAS NMR spectroscopy of pheochromocytomas and paragangliomas detects SDH deficiency: clinical and pathophysiological implications.
Recent advances in genetics revealed that 25% to 30% of head and neck paragangliomas (PGLs) are inherited tumors associated with germline mutation, mainly in the succinate dehydrogenase (SDH) gene.
Patients with germline mutations in one of the SDH genes are at substantially increased risk of developing paragangliomas, pheochromocytomas (pheos), and other tumors (all combined referred to as SDH-related tumors).
Germ line heterozygous mutations in the structural subunit genes of mitochondrial complex II (succinate dehydrogenase; SDH) and the regulatory gene SDHAF2 predispose to paraganglioma tumors which show constitutive activation of hypoxia inducible pathways.