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BIOMARKER:

SDHB mutation

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Other names: SDHB, Succinate Dehydrogenase Complex Iron Sulfur Subunit B, Iron-Sulfur Subunit Of Complex II, Succinate Dehydrogenase [Ubiquinone] Iron-Sulfur Subunit, Mitochondrial, Succinate Dehydrogenase Complex, Subunit B, Iron Sulfur (Ip), SDH1, SDH, Succinate Dehydrogenase Complex Subunit B, Iron Sulfur (Ip), Succinate Dehydrogenase [Ubiquinone] Iron-Sulfur Subunit, SDHIP, CWS2, PGL4, SDH2
Entrez ID:
3d
Clinical • New P1 trial • Combination therapy
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VHL (von Hippel-Lindau tumor suppressor) • EPAS1 (Endothelial PAS domain protein 1) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • SDHC (Succinate Dehydrogenase Complex Subunit C) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A) • SDHAF2 (Succinate Dehydrogenase Complex Assembly Factor 2) • SDHD (Succinate Dehydrogenase Complex Subunit D)
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VHL mutation • SDHB mutation
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everolimus • spartalizumab (PDR001) • DFF332 • taminadenant (NIR178)
9d
P2, N=25, Recruiting, Columbia University | Trial primary completion date: Jan 2021 --> Dec 2021
Trial primary completion date
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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VHL mutation • SDHB mutation
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Inlyta (axitinib)
16d
Compared to females, males with CBT resection were found to have more SDHB mutations and worse relapse-free survival rates, which may lead to the deterioration of prognosis. Tumor size and Shamblin classification cannot predict the overall survival rate of patients with excised CBTs.
Journal
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
17d
Syndromic PGLs are rare conditions; surgery is the treatment of choice. Adrenal PGL requires laparoscopic adrenalectomy with transperitoneal lateral approach as gold standard. For genetic syndrome such as MEN2 and VHL, laparoscopic cortical sparing adrenalectomy of at least one gland should be considered.
Journal
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RET (Ret Proto-Oncogene) • NF1 (Neurofibromin 1) • VHL (von Hippel-Lindau tumor suppressor) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • SDHD (Succinate Dehydrogenase Complex Subunit D)
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RET mutation • VHL mutation • SDHB mutation
21d
Clinical • Journal
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
1m
This treatment was repeated 6 years later due to disease progression and the patient, who is currently 49 years old, remains alive and in good overall clinical condition at 8 years of follow-up after the original presentation at our unit. The growing armamentarium of imaging methods available for such patients may inform decision making regarding choice of the optimal treatment approach, potentially contributing to improved outcomes.
Journal
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
2ms
In addition, PGLs with SDHB loss had significantly increased expression of PCA3 compared to tumors with intact SDHB expression. Our findings suggest that specific lncRNAs may be involved in the SDHx signaling pathways in the tumorigenesis and in the development of PPGL.
Journal
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MALAT1 (Metastasis associated lung adenocarcinoma transcript 1) • HOTAIR (HOX Transcript Antisense RNA) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • PCA3 (Prostate cancer associated 3)
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SDHB mutation
2ms
Paragangliomas in paediatric population are almost always due to a germline mutation, being the ones in genes coding Succinate Dehydrogenase (SDH) subunits collectively the most common cause of hereditary paraganglioma-pheochromocytoma. Even in the absence of a family history, genetic testing should be offered for all paediatric patients with paragangliomas and their family. Patients with SDHB mutation should maintain a lifelong, regular surveillance.
Clinical
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NCAM1 (Neural cell adhesion molecule 1) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • CHGA (Chromogranin A) • SYP (Synaptophysin)
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SDHB mutation
2ms
According to the literature, one of the main factors, indicat- ing risk for metastatic paragangliomas/pheochromocytomas, is the SDHB mutation. However, in the study case, we have not identified variants in any known susceptibility genes. In primary tumour and metastasis, we detected common somatic likely pathogenic variants in six genes, when much more novel genes were mutated only in metastasis.
Clinical
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NF1 (Neurofibromin 1) • EPAS1 (Endothelial PAS domain protein 1) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • PERK (Pancreatic EIF2-Alpha Kinase) • TMEM127 (Transmembrane Protein 127) • EGLN1 (Egl-9 Family Hypoxia Inducible Factor 1) • KIF1B (Kinesin Family Member 1B) • SDHAF2 (Succinate Dehydrogenase Complex Assembly Factor 2)
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SDHB mutation
2ms
Here, we focus on the role of ROS production in PHEO and PGL, predominantly in SDHB-mutated cases. We discuss potential strategies and approaches to anticancer therapies by enhancing ROS production in these difficult-to-treat tumors.
Journal
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
2ms
In conclusion, SDHB-negative IHC is a cost-effective and reliable method to predict SDHx mutations. However, in the case of weakly positive SDHB staining, an additional gene study should be considered.
Clinical • Journal
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • SDHD (Succinate Dehydrogenase Complex Subunit D)
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SDHB mutation
2ms
In our study, the factors that were possibly related to a worse prognosis were the GAPP score grade, size, and location. While these tumours are biologically unpredictable, multivariable prognostic tools, such as the GAPP score, can aid in outlining an appropriate patient’s management. Despite its small sample size, our case series’ findings are consistent with current reported data.
Clinical • Review
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • SDHD (Succinate Dehydrogenase Complex Subunit D)
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SDHB mutation
2ms
Despite a superficial similarity, FHRCC and SDHRCC represent distinct molecular entities with unique genetic and metabolic abnormalities.
Tumor Mutational Burden
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TMB (Tumor Mutational Burden) • FH (Fumarate Hydratase) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
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MET mutation • SDHB mutation
4ms
Journal
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
4ms
They also highlight high-dose ascorbate as a promising therapeutic strategy for SDHB-related cancers. SIGNIFICANCE: Loss of different succinate dehydrogenase subunits can lead to different cell and tumor phenotypes, linking stronger 2-OG-dependent dioxygenases inhibition, iron overload, and ROS accumulation following SDHB mutation.
Journal
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
4ms
Further metabolomic analysis of PGL-626 cells showed that metabolites involved in central carbon metabolism in cancer and sphingolipid signaling pathways, pantothenate and CoA biosynthesis, and tryptophan and carbon metabolism were significantly altered after metformin treatment. Thus, this study provides insights into the molecular mechanisms underlying HNPGL tumorigenesis and identifies target correction of metabolic abnormalities as a novel therapeutic approach for this disease.
Journal
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
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metformin
4ms
In this study, no risk factors for malignancy have been established; therefore, we recommend follow-up of all patients diagnosed with paraganglioma.
Clinical • Journal
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
4ms
Orbital paraganglioma with SDHB loss is an extremely rare clinical entity. Loss of complex II protein function leads to loss of aerobic respiration in the neoplastic tissue, and dependence on alternate anaerobic energy metabolism. This provides survival benefit to neoplastic cells and leads to pseudohypoxia, activation of HIF1 and VEGF mediated vascular proliferation.
Clinical
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HIF1A (Hypoxia inducible factor 1, alpha subunit) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • SYP (Synaptophysin)
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SDHB mutation
5ms
In our cohort, SDHB mutation and pseudohypoxia subtype were significantly associated with poor overall survival. In conclusion, subtyping of mutation profile can be helpful in aggressive PPGL patients with heterogeneous prognosis to make relevant follow-up plan and achieve proper treatment.
Journal • Tumor Mutational Burden
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TMB (Tumor Mutational Burden) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NF1 (Neurofibromin 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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HRAS mutation • NF1 mutation • SDHB mutation • SETD2 mutation
5ms
In terms of treatment, apart from surgical and radiotherapeutic interventions, new therapeutic measures such as gene targeted therapy have contributed very sparsely. With the lack of standardized protocols, management of patients with multiple HNPGLs still remains very challenging, especially in those with sporadic or malignant forms of the disease.
Clinical • Journal
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
5ms
The main prognostic factors of the malignant pheochromocytomas are a large tumor volume, the existence or number of visceral metastases, and the presence of a mutation in the SDHB (Succinate dehydrogenase B) gene.
Journal
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
5ms
Compared with MPP patients without SDHB mutations, MPP patients with SDHB mutations were younger at onset, diagnosis, or metastasis; had a higher incidence of synchronous metastases, higher ratio of paraganglioma, and higher Ki-67 index; had a shorter postoperative progression-free survival; and were more likely to develop bone metastasis or sole liver metastasis. Our results suggest that patients with SDHB mutations should be identified early and monitored regularly to achieve optimal clinical outcomes.
Clinical • Journal
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
5ms
On immunohistochemistry and Western blotting, the 11 tumors with SNVs of SDHA gene had higher protein expression for nuclear factor E2-related factor 2 (Nrf2) compared to the 19 tumors without the mutation (p < 0.01). These observations suggest that SDHA gene mutations might be associated with a subset of RCC.
Journal
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • SDHC (Succinate Dehydrogenase Complex Subunit C)
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SDHB mutation • SDHC mutation
5ms
Clinical • New P1 trial • Combination therapy • IO biomarker
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VHL (von Hippel-Lindau tumor suppressor) • EPAS1 (Endothelial PAS domain protein 1) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • SDHC (Succinate Dehydrogenase Complex Subunit C) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A) • SDHAF2 (Succinate Dehydrogenase Complex Assembly Factor 2) • SDHD (Succinate Dehydrogenase Complex Subunit D)
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VHL mutation • SDHB mutation
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everolimus • spartalizumab (PDR001) • DFF332 • taminadenant (NIR178)
5ms
Notably, the RET-mutant effect required the presence of dexamethasone while the SDHB-mutant effect required its absence, providing a plausible explanation for the tumor location preference. In contrast, the PPGL-predisposing VHL mutations had no effect on proliferation and GIPC2 expression but caused p53 downregulation and reduced apoptosis in chromaffin cells compared with wild-type VHL. Thus, our study raises the importance of cortical hormone in PPGL development, and GIPC2 as a novel tumor suppressor provides a unified molecular mechanism for the tumorigenesis of both sporadic and hereditary tumors of Clusters 1A and 2A concerning SDHB and RET, but not tumors of Cluster 1B concerning VHL and other clusters.
Journal
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TP53 (Tumor protein P53) • RET (Ret Proto-Oncogene) • NF1 (Neurofibromin 1) • VHL (von Hippel-Lindau tumor suppressor) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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TP53 mutation • RET mutation • VHL mutation • TP53 expression • HIF1A expression • SDHB mutation • CDKN1B expression
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dexamethasone
6ms
Patients with SDHx mutation, particularly SDHB, have increased risk of developing metastatic PGLs. Consequently, these individuals require long-term surveillance given the risk for developing new tumors or disease recurrence, even years to decades after primary tumor resection. Surgical management of spinal metastatic PGL involves correcting spinal instability, minimizing tumor burden, and alleviating epidural cord compression. In patients with metastatic PGL of the spine, genetic testing should be considered.
Clinical • Review • Journal
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
7ms
Patients with a succinate dehydrogenase subunit B (SDHB ) gene mutations are predisposed to developing paraganglioma/pheochromocytoma. The tumors produce catecholamines, but can be biochemically silent as in our patient. They are inherited in an autosomal dominant manner.
SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
7ms
Most of our patients had a HNPG with initial symptoms caused by compression and invasion of adjacent structures. Previous studies reported a founder mutation in the SDHB gene (15678bp deletion) in Portuguese PG patients, which was found in 2 of our patients. This is an unicentric analysis with a small sample thus its limitations should be noted.
Clinical
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
8ms
While the variation in the forms manifested, such as TTC or inverted TTC, can be attributed to anatomical differences in the sympathetic innervation of the heart and individual differences in adrenergic receptor distribution, further details are unknown. The incidence and severity of TTC in PHEO or PGL with/without SDHB mutation are issues for future Study.
Clinical
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
8ms
SDH-deficient GISTs comprise a subgroup of a relatively rare tumor type and show a number of clinically and biologically unique features, especially for infants. It is of great importance to developing new therapeutic targets and novel specific drugs.
Clinical • Review • Journal
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KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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PDGFRA mutation • SDHB mutation
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imatinib
8ms
The lncRNAs MALAT1 , PCA3 , and HOTAIR are upregulated in metastatic PPGLs. SDHB loss in PGLs is associated with increased expression of PCA3. In addition, SDHB loss is a useful marker to predict poor prognosis in PGLs.
MALAT1 (Metastasis associated lung adenocarcinoma transcript 1) • HOTAIR (HOX Transcript Antisense RNA) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • PCA3 (Prostate cancer associated 3)
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SDHB mutation
9ms
He was referred for genetic testing which demonstrate no evidence of mutation in FH, SDHAF2, SDHB/C/D, RET, MAX, TMEM127 and VHL gene.He was commenced on levothyroxine replacement at a dose of 150micrograms OD.His urine metanephrines is 178.1pmol/L (0-510), urine normetanephrines 192.9pmol/L (0-1180) and 3-methoxytyramine <75pmol/ L (0-180) (all normal)...Conclusion Due to the rarity of these tumours, their natural history is mostly unknown. Nevertheless, postoperative surveillance should include plasma or urinary metanephrines and ultrasonography.
VHL (von Hippel-Lindau tumor suppressor) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • TMEM127 (Transmembrane Protein 127)
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RET mutation • SDHB mutation
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thyroxine
9ms
This case illustrates the importance of following up on incidental radiographic findings and adds to the limited literature on sporadic UBPGLs, an uncommon, yet potentially life-threatening tumor. The diagnosis of these tumors is especially challenging when patients present with non-specific symptoms. Fortunately, in our case, the imaging study clued us into the possibility of a PGL.
Clinical
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SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation
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Octreosphere (octreotide extended release)
9ms
Advancements in genetics have led to improved understanding of the molecular etiologies of pheochromocytomas. A number of genetic defects are associated with PC and RCC, including SDHB mutations type 4, VHL and familial pheochromocytoma. Our case underscores the high morbidity and mortality in patients with metastatic PC with RCC and perhaps the catastrophic outcomes in such patients.
Clinical
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VHL (von Hippel-Lindau tumor suppressor) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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VHL mutation • SDHB mutation
9ms
For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO 2021.
SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B)
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SDHB mutation