Functional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma

J Clin Endocrinol Metab. 2002 Oct;87(10):4771-4. doi: 10.1210/jc.2002-020525.


Three genes encoding for mitochondrial complex II proteins are linked to hereditary paraganglioma. We have recently shown that an inactivation of the SDHD gene is associated with a complete loss of mitochondrial complex II activity and a stimulation of the angiogenic pathway (Gimenez-Roqueplo, A. P., J. Favier, P. Rustin, J. J. Mourad, P. F. Plouin, P. Corvol, A. Rötig, and X. Jeunemaitre, 2001, Am J Hum Genet 69:1186-1197). Here, we relate the case of a malignant sporadic pheochromocytoma induced by a germline missense mutation of the SDHB gene. Within the tumor, a loss of heterozygosity at chromosome 1pter led to a null SDHB allele and to a complete loss of complex II enzymatic activity. In situ hybridization and immunohistochemistry experiments showed a high expression of hypoxic-angiogenic responsive genes, similar to that previously observed in inherited-SDHD tumors. This observation highlights the role of the complex II mitochondrial genes in the oxygen-sensing pathway and in the regulation of angiogenesis of neural crest-derived tumors.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Gland Neoplasms / enzymology
  • Adrenal Gland Neoplasms / genetics*
  • Basic Helix-Loop-Helix Transcription Factors
  • Chromosomes, Human, Pair 1
  • DNA Mutational Analysis
  • Electron Transport Complex II
  • Endothelial Growth Factors / genetics
  • Female
  • Gene Expression
  • Germ-Line Mutation
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Iron-Sulfur Proteins / genetics*
  • Iron-Sulfur Proteins / physiology
  • Loss of Heterozygosity
  • Lymphokines / genetics
  • Middle Aged
  • Multienzyme Complexes / deficiency
  • Multienzyme Complexes / genetics
  • Mutation*
  • Mutation, Missense
  • Oxidoreductases / deficiency
  • Oxidoreductases / genetics
  • Pheochromocytoma / enzymology
  • Pheochromocytoma / genetics*
  • Protein Subunits
  • RNA, Messenger / analysis
  • Sequence Analysis, DNA
  • Succinate Dehydrogenase / deficiency
  • Succinate Dehydrogenase / genetics
  • Tomography, X-Ray Computed
  • Trans-Activators / genetics
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Basic Helix-Loop-Helix Transcription Factors
  • Endothelial Growth Factors
  • Iron-Sulfur Proteins
  • Lymphokines
  • Multienzyme Complexes
  • Protein Subunits
  • RNA, Messenger
  • Trans-Activators
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • endothelial PAS domain-containing protein 1
  • Oxidoreductases
  • Electron Transport Complex II
  • SDHB protein, human
  • Succinate Dehydrogenase