Succinate Dehydrogenase-deficient Tumors: Diagnostic Advances and Clinical Implications

@article{Barletta2012SuccinateDT,
  title={Succinate Dehydrogenase-deficient Tumors: Diagnostic Advances and Clinical Implications},
  author={Justine A. Barletta and Jason L. Hornick},
  journal={Advances In Anatomic Pathology},
  year={2012},
  volume={19},
  pages={193–203}
}
Just over 10 years ago, germline mutations in SDHD, a gene that encodes 1 of the 4 proteins of the succinate dehydrogenase (SDH) complex, were reported in a subset of patients with hereditary paraganglioma-pheochromocytoma syndrome. Since that time, rapid discoveries have been made in this area. It is now recognized that all of the SDH genes are involved in the tumorigenesis of not only paragangliomas/pheochromocytomas, but also other tumor types, most notably gastrointestinal stromal tumors… 
Succinate dehydrogenase deficient gastrointestinal stromal tumors (GISTs) - a review.
Identification of Succinate Dehydrogenase–deficient Bladder Paragangliomas
TLDR
The aim of this study was to determine the rate of SDH deficiency in bladder paragangliomas, and to identify SDH-deficient tumors, as the presence of an SDH mutation has prognostic implications and is important in guiding genetic counseling.
Succinate dehydrogenase-deficient renal cell carcinoma: detailed characterization of 11 tumors defining a unique subtype of renal cell carcinoma
TLDR
A monomorphic oncocytic renal tumor with solid architecture, cytoplasmic inclusions of flocculent material, and intratumoral mast cells should prompt evaluation of SDH status, as it may have implications for screening the patient and relatives.
Succinate Dehydrogenase A (SDHA) Gene Mutation in Renal Cell Carcinoma: A New Subset of Hereditary Renal Cancer
TLDR
Investigating SDHA/B/C/D gene mutations in 72 human RCCs by targeted next-generation sequencing suggested that germline SDHA gene mutations might be linked to hereditary RCC associated with mitochondrial dysfunction.
Genetic and epigenetic alterations of SDH genes in patients with sporadic succinate dehydrogenase‐deficient gastrointestinal stromal tumors
TLDR
It is suggested that SDH gene mutations and promoter methylation may contribute to the loss of SDH protein expression in sporadic SDH‐deficient GISTs.
Single nucleotide variants of succinate dehydrogenase A gene in renal cell carcinoma
TLDR
Observations suggest that SDHA gene mutations might be associated with a subset of RCC.
SDH-deficient renal cell carcinoma associated with biallelic mutation in succinate dehydrogenase A: comprehensive genetic profiling and its relation to therapy response
TLDR
A case of genetically characterized SDH-deficient RCC caused by biallelic (germline plus somatic) SDHA mutations is described and how the genetic results provide a rationale for their effectiveness is highlighted.
Succinate dehydrogenase deficiency is associated with decreased 5-hydroxymethylcytosine production in gastrointestinal stromal tumors: implications for mechanisms of tumorigenesis
TLDR
It is suggested that SDH deficiency may promote tumorigenesis through accumulation of succinate and inhibition of dioxygenase enzymes, and inhibition of TET activity may, in turn, alter global DNA methylation and gene expression in SDH-deficient tumors.
Succinate dehydrogenase-deficient gastrointestinal stromal tumors.
TLDR
In WT GISTs without succinate dehydrogenase activity, upregulation of hypoxia-inducible factor 1α may lead to increased growth signaling through IGF1R and vascular endothelial growth factor receptor (VEGFR).
Succinate Dehydrogenase-Deficient Renal Cell Carcinoma.
TLDR
The prognosis is good for low-grade tumors but worse for tumors with high-grade nuclei, sarcomatoid change, or coagulative necrosis, and long-term follow-up is indicated.
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