Isocitrate dehydrogenase mutations are rare in pheochromocytomas and paragangliomas.
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.
Gaal
José
J
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
Burnichon
Nelly
N
Korpershoek
Esther
E
Roncelin
Isabelle
I
Bertherat
Jérôme
J
Plouin
Pierre-François
PF
de Krijger
Ronald R
RR
Gimenez-Roqueplo
Anne-Paule
AP
Dinjens
Winand N M
WN
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
D007521:Isocitrate Dehydrogenase