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ABSTRACT: Context
Pheochromocytomas and paragangliomas are genetically heterogeneous tumors of neural crest origin. Approximately half of these tumors activate a pseudohypoxic transcription response, which is due in a minority of the cases to germline mutations of the VHL gene or the genes encoding subunits of the metabolic enzyme succinate dehydrogenase (SDH), SDHB, SDHC, or SDHD. However, the genetic basis of the hypoxic-like profile of the remaining tumors is undetermined. Mutations in genes involved in the energy metabolism, isocitrate dehydrogenase 1 (IDH1) and -2 (IDH2) and SDHAF2, a component of SDH, can mimic a pseudohypoxic state.Design
We examined the sequence spanning the mutation-susceptible codons 132 of IDH1 and 172 of IDH2, and the entire coding region of SDHAF2, in 104 pheochromocytomas and paragangliomas, including tumors with a pseudohypoxic expression profile.Results
We did not find mutations in IDH1, IDH2, or SDHAF2 in any of the tumors in this cohort.Conclusion
Conserved residues of IDH1 and IDH2 or the SDHAF2 gene are not frequently mutated in pheochromocytomas and paragangliomas. The molecular basis for activation of a hypoxic response in the majority of tumors without VHL or SDH mutations remains to be defined.
SUBMITTER: Yao L
PROVIDER: S-EPMC2841540 | biostudies-literature | 2010 Mar
REPOSITORIES: biostudies-literature
Yao Li L Barontini Marta M Niederle Bruno B Jech Marion M Pfragner Roswitha R Dahia Patricia L M PL
The Journal of clinical endocrinology and metabolism 20100203 3
<h4>Context</h4>Pheochromocytomas and paragangliomas are genetically heterogeneous tumors of neural crest origin. Approximately half of these tumors activate a pseudohypoxic transcription response, which is due in a minority of the cases to germline mutations of the VHL gene or the genes encoding subunits of the metabolic enzyme succinate dehydrogenase (SDH), SDHB, SDHC, or SDHD. However, the genetic basis of the hypoxic-like profile of the remaining tumors is undetermined. Mutations in genes in ...[more]