title: Isocitrate dehydrogenase mutations are rare in pheochromocytomas and paragangliomas.
abstract: BACKGROUND
  Paragangliomas and pheochromocytomas are neuroendocrine tumors that occur sporadically and in the context of inherited tumor syndromes including hereditary paraganglioma-pheochromocytoma syndrome and von Hippel-Lindau disease (VHL). The paraganglioma-pheochromocytoma syndrome is caused by germline-inactivating mutations in the mitochondrial succinate dehydrogenase (SDH) genes SDHB, SDHC, SDHD, or SDHAF2, and VHL is the result of inactivating VHL gene mutations. In SDH- and VHL-related paraganglioma and pheochromocytoma, hypoxia-inducible factor (HIF) stabilization has been described as the causal oncogenic event. Recently, HIF activation has also been found in glioblastoma multiforme, as the result of somatic mutational inactivation of the isocitrate dehydrogenase (IDH) type 1 or type 2 enzymes. These findings suggest that inactivating IDH1 and IDH2 mutations might also play a role in paraganglioma and pheochromocytoma tumorigenesis, especially in non-SDH- or non-VHL-related tumors.
  
  
  METHODS
  We investigated 365 pheochromocytomas and paragangliomas, including 269 sporadic tumors without SDH or VHL gene mutations, for mutations in IDH1 and IDH2. Only codons 132 and 172 were screened because these are the ones exclusively involved.
  
  
  RESULTS
  In one of 131 paragangliomas, a somatic heterozygous IDH1 p.Arg132Cys mutation was detected in a sporadic carotid paraganglioma diagnosed in a 61-yr-old woman. No mutations were found in 234 pheochromocytomas.
  
  
  CONCLUSIONS
  IDH mutations are very rare in paragangliomas and pheochromocytomas and do not appear to play an important role in oncogenic HIF activation known to be present in these tumors.
authors.affiliation: Department of Pathology, Josephine Nefkens Institute, Room Ae304, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. j.gaal@erasmusmc.nl
authors.forename: José
authors.initials: J
authors.lastname: Gaal
authors.forename: Nelly
authors.initials: N
authors.lastname: Burnichon
authors.forename: Esther
authors.initials: E
authors.lastname: Korpershoek
authors.forename: Isabelle
authors.initials: I
authors.lastname: Roncelin
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Plouin
authors.forename: Ronald R
authors.initials: RR
authors.lastname: de Krijger
authors.forename: Anne-Paule
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
authors.forename: Winand N M
authors.initials: WN
authors.lastname: Dinjens
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010235:Paraganglioma / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D007521:Isocitrate Dehydrogenase