Recent advances in the genetics of phaeochromocytoma and functional paraganglioma

Clin Exp Pharmacol Physiol. 2008 Apr;35(4):376-9. doi: 10.1111/j.1440-1681.2008.04881.x.

Abstract

1. Recent clinical and fundamental research studies have revolutionized our understanding of the genetics of phaeochromocytoma (PH) and functional paraganglioma (FPGL). It was widely thought that only 10% of PH patients had familial disease and that the malignant phenotype of PH could not be diagnosed before occurrence of the first metastasis. 2. Human genetic studies have now shown that 25-30% of patients have hereditary PH due to a germline mutation in the SDHB, SDHD, VHL, RET or NF1 gene and that the identification of a germline SDHB mutation is associated with a high risk of malignancy and a poor prognosis in PH/PGL patients. 3. Fundamental research studies have shown that SDH genes are tumour suppressor genes and that succinate dehydrogenase inactivation induces abnormal stimulation of the hypoxia-angiogenesis pathway. 4. Finally various fundamental research studies, conducted through the Cortico and Medullo-surrenale: les Tumeurs Endocrines (COMETE) network in France and by other groups worldwide, have produced new recommendations for genetic counselling and testing and for the management of PH patients. They have also improved our understanding of the molecular mechanisms involved in PH tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Counseling
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Iron-Sulfur Proteins / genetics
  • Mitochondria / metabolism
  • Mutation
  • Neovascularization, Pathologic / genetics
  • Paraganglioma / genetics*
  • Pheochromocytoma / genetics*
  • Proto-Oncogene Proteins c-ret / genetics
  • Succinate Dehydrogenase / genetics
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics

Substances

  • Genetic Markers
  • Iron-Sulfur Proteins
  • SDHD protein, human
  • SDHB protein, human
  • Succinate Dehydrogenase
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • VHL protein, human