An update on the genetics of paraganglioma, pheochromocytoma, and associated hereditary syndromes

A. P. Gimenez-Roqueplo, P. L. Dahia, M. Robledo

Research output: Contribution to journalReview articlepeer-review

229 Scopus citations


Pheochromocytomas (PCCs) and paragangliomas (PGLs) are catecholamine- secreting tumors of neural crest origin. Once collectively known as the 10% tumor', based on the frequency of inherited forms of the disease, they are now referred to as the 10-gene tumor', based on the number of susceptibility genes identified to date. Most familial cases of pheochromocytoma and/or paraganglioma and 10-20% sporadic cases carry germline mutations in VHL, RET, NF1, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, or MAX. The finding of somatic mutations in VHL and RET in an additional 10-15% of tumors has brought the proportion of all patients with PCC and/or PGL due to a genetic disruption in these genes to approximately one half. These findings impact on the clinical management of patients. The diversity in the genetic etiology has transcription correlates, which are reflected in the 2 main transcription signatures underlying these mutations: a pseudohypoxic cluster (VHL and SDH gene mutation carriers) and a cluster rich in kinase receptor signaling and protein translation pathways (RET, NF1, TMEM127 and MAX mutation carriers). Recognition of these clusters offers clues to better understand tumor pathogenesis as well as a rationale for the development of targeted therapies. In this report we provide an overview of the transcription-based classification of PCCs and PGLs, an update on the more recently identified susceptibility genes and an outline of current gaps in this research field as well as challenges for the coming years.

Original languageEnglish (US)
Pages (from-to)328-333
Number of pages6
JournalHormone and Metabolic Research
Issue number5
StatePublished - 2012


  • MAX
  • SDHB
  • SDHD
  • TMEM127
  • VHL
  • genetics

ASJC Scopus subject areas

  • Biochemistry, medical
  • Endocrinology
  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism


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