Succinate dehydrogenase (SDH) is an enzyme complex composed of four major subunits (A,B, C and D). It is localized on the inner side of the mitochondrial membrane and is part of the citric acid cycle and respiratory chain. The germinal mutations lead to the familial paraganglioma syndrome. Somatic inactivation of the second allele of the mutated gene causes the inactivation of the encoded subunit, destabilization of the whole complex and also leads to the loss of its enzymatic function, which significantly affects the cell oncogenesis.

A small part of GIST is associated with the loss of function of SDH. GISTs may carry germline mutations of the gene encoding one of the SDH subunits (i.e. SDHA, SDHB, SDHC, SDHD) either as part of Carney - Stratakis syndrome (familial paraganglioma - GIST syndrome) or as a sporadic "wild type" GIST.

Examination

Examination in our laboratory, we perform the examination of SDHB, SDHC a SDHD genes using PCR and direct sequencing.

References

1. Burnichon N, Rohmer V, Amar L, et al. The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas. J Clin Endocrinol Metab 2009; 94(8): 2817-2827.
2. Pasini B, McWhinney SR, Bei T, et al. Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD. Eur J Hum Genet 2008; 16(1): 79-88.
3. Janeway KA, Kim SY, Lodish M, et al. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc Natl Acad Sci U S A 2011; 108(1): 314-318.
4. Wang JH, Lasota J, Miettinen M.: Succinate Dehydrogenase Subunit B (SDHB) Is Expressed in Neurofibromatosis 1-Associated Gastrointestinal Stromal Tumors (Gists): Implications for the SDHB Expression Based Classification of Gists. J Cancer. 2011 Feb 16;2:90-3.