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SDHB-deficient GISTs and GISTS associated with Carney Triad reveal abnormal mitochondrial ultrastructure: a comparative study including observations in heterozygous Sdhb-deficient mice

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • E Szarek
  • M Tsokos
  • A Giubellino
  • M Abu-Asab
  • E Ball
  • L Dye
  • P Xekouki
  • F Faucz
  • K Pacak
  • J Carney
  • CA Stratakis


Carney Triad(CTr) describes the association of paragangliomas(PGL) and gastrointestinal stromal tumors(GISTs) with other lesions including pheochromocytomas and adrenocortical tumors. The gene(s) causing CTr remain(s) unknown. Patients with dyad of PGL and GISTs (Carney-Stratakis syndrome/CSS) without other tumors contain loss-of-function(LOF) mutations in SDHx subunit genes, commonly SDHB (mitochondrial protein). Mitochondria function in metabolism and free radical generation; mitochondrial dysfunction can be correlated with tumor progression. SDHB LOF affecting mitochondrial function may lead to tumorigenesis, by inducing angiogenesis and glycolysis. We identified aberrant mitochondrial morphology in PGLs with SDHx mutations, providing the impetus for current investigations and asked: is mitochondrial morphology comparable in patients with GISTs harboring SDHx mutations to those without, mainly CTr patients. Patients with CTr-associated GISTs, SDHx mutations (SDHB, SDHC) and patients with PGL were included. Examination of mitochondria from Sdhb+/- mouse small intestine by electron microscopy was included. In patients, epithelioid GISTs were characterized by plump cells containing centrally located round nucleus and prominent nucleoli. Cytoplasm contained increased mitochondria numbers with highly abnormal structure (devoid of cristae, structural abnormalities and variable size). Similar mitochondrial ultrastructure was identified in mice. Data indicate SDHB-deficient GISTs, and those associated with CTr contain abnormal mitochondrial ultrastucture contributing to tumor-associated damage.

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