Transcription association of VHL and SDH mutations link hypoxia and oxidoreductase signals in pheochromocytomas

Research output: Chapter in Book/Report/Conference proceedingConference contribution

39 Scopus citations


Pheochromocytomas and paragangliomas are neural-crest-derived tumors that arise from mutations in RET, VHL, NF1, and in the genes-encoding succinate dehydrogenase (SDH) subunits B (SDHB), C (SDHC), and D (SDHD). Despite their genetic diversity, these tumors cannot be clearly distinguished on the basis of their primary mutation. We recently identified two major transcriptional programs embedded within familial and sporadic pheochromocytomas and paragangliomas using global expression profiling. This review will summarize the major results of these studies and discuss their implications. The transcription data revealed that: (a) tumors with mutations in VHL, SDHB, and SDHD genes share a transcription signature of hypoxia, angiogenesis, and oxidoreductase imbalance; (b) SDHB protein is suppressed in tumors with mutations in SDHB and SDHD, and also in a subset of tumors with VHL mutations; and (c) HIF1α is involved in the SDHB downregulation observed in these tumors. These results are consistent with the existence of a close interconnection between the VHL and SDH pathways mediated predominantly by hypoxia and oxidoreductase signals. It further suggests that low SDHB levels indicative of impaired mitochondrial complex II function may be a shared element of these pheochromocytomas. SDHB may thus constitute a marker for tumors with abnormal hypoxic profile.

Original languageEnglish (US)
Title of host publicationPheochromocytoma
Subtitle of host publicationFirst International Symposium
PublisherBlackwell Publishing Inc.
Number of pages13
ISBN (Print)1573315974, 9781573315975
StatePublished - Aug 2006

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632


  • Hypoxia
  • Hypoxia-inducible factor (HIF)
  • Hypoxia-inducible factor subunit
  • Microarray
  • Multiple endocrine neoplasia Type 2 (MEN 2)
  • Mutation
  • Neurofibromatosis Type 1 (NF1)
  • Oxidative stress
  • Oxidoreductase
  • Paraganglioma
  • Pathway intersection
  • Pheochromocytoma

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience
  • History and Philosophy of Science


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