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Genetics of Pheochromocytoma

  1. Victoria L Martucci,
  2. Karel Pacak

Published Online: 15 APR 2014

DOI: 10.1002/9780470015902.a0025302



How to Cite

Martucci, V. L. and Pacak, K. 2014. Genetics of Pheochromocytoma. eLS. .

Author Information

  1. National Institutes of Health, Bethesda, Maryland, USA

Publication History

  1. Published Online: 15 APR 2014


Pheochromocytoma (PHEO) and paraganglioma (PGL) are closely related neuroendocrine tumours of the chromaffin tissues of the sympathetic and parasympathetic nervous system. These rare tumours have a strong genetic component, with underlying germline and somatic mutations in one of 17 genes found in approximately 50%. Clinical presentations of PHEO/PGL vary based on the affected gene, and understanding these differences can help guide genetic testing, an important part of PHEO/PGL patient management. Despite the differences in presentation and gene function, all 17 genes may affect a single pathway. Particularly, recent proposals have focused on hypoxia-inducible factors (HIFs) as key players in PHEO/PGL, due to the known pseudohypoxic environment found in these tumours and the central role played by HIFs in cellular processes. By linking the susceptibility genes to a central potential therapeutic target like HIF, new treatment methods could soon be introduced to improve the outcomes of PHEO/PGL patients.

Key Concepts:

  • Pheochromocytomas and paragangliomas have the strongest genetic component of any endocrine tumour; half or more are linked to germline and somatic mutations in 17 genes.

  • The clinical presentations associated with each gene vary, particularly with regard to tumour location, multiplicity, biochemical phenotype, average patient age at diagnosis and risk of metastases.

  • Genetic testing is an essential component of PHEO/PGL management, but can be costly and time-consuming; newer techniques to resolve these limitations are being explored.

  • Messenger RNA expression profiles can help broadly classify PHEO/PGL into two well-established clusters based on their broader mechanistic errors.

  • Additional clustering mechanisms are being proposed based on other analyses, including miRNA, transcriptomic, metabolomic and proteomic studies.

  • Beyond clustering, unifying theories to link PHEO/PGL susceptibility genes have been proposed to link all 17 genes to a common signalling pathway, focusing particularly on the processes of apoptosis and hypoxia response.

  • Identifying common targets between the genes could aid in the identification of novel treatment strategies for patients with these rare neuroendocrine tumours.


  • genetics;
  • pheochromocytoma;
  • paraganglioma;
  • hypoxia;
  • hypoxia-inducible factors;
  • succinate dehydrogenase