title: Functional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma.
abstract: Three genes encoding for mitochondrial complex II proteins are linked to hereditary paraganglioma. We have recently shown that an inactivation of the SDHD gene is associated with a complete loss of mitochondrial complex II activity and a stimulation of the angiogenic pathway (Gimenez-Roqueplo, A. P., J. Favier, P. Rustin, J. J. Mourad, P. F. Plouin, P. Corvol, A. Rötig, and X. Jeunemaitre, 2001, Am J Hum Genet 69:1186-1197). Here, we relate the case of a malignant sporadic pheochromocytoma induced by a germline missense mutation of the SDHB gene. Within the tumor, a loss of heterozygosity at chromosome 1pter led to a null SDHB allele and to a complete loss of complex II enzymatic activity. In situ hybridization and immunohistochemistry experiments showed a high expression of hypoxic-angiogenic responsive genes, similar to that previously observed in inherited-SDHD tumors. This observation highlights the role of the complex II mitochondrial genes in the oxygen-sensing pathway and in the regulation of angiogenesis of neural crest-derived tumors.
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000201:enzymology / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins; D002878:Chromosomes, Human, Pair 1; D004252:DNA Mutational Analysis; D042963:Electron Transport Complex II; D016228:Endothelial Growth Factors / Q000235:genetics; D005260:Female; D015870:Gene Expression; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007506:Iron-Sulfur Proteins / Q000235:genetics* / Q000502:physiology; D019656:Loss of Heterozygosity; D008222:Lymphokines / Q000235:genetics; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000172:deficiency / Q000235:genetics; D009154:Mutation; D020125:Mutation, Missense; D010088:Oxidoreductases / Q000172:deficiency / Q000235:genetics; D010673:Pheochromocytoma / Q000201:enzymology / Q000235:genetics*; D021122:Protein Subunits; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D013385:Succinate Dehydrogenase / Q000172:deficiency / Q000235:genetics; D014057:Tomography, X-Ray Computed; D015534:Trans-Activators / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D042963:Electron Transport Complex II; D016228:Endothelial Growth Factors; D007506:Iron-Sulfur Proteins; D008222:Lymphokines; D009097:Multienzyme Complexes; D010088:Oxidoreductases; D021122:Protein Subunits; D012333:RNA, Messenger; D013385:Succinate Dehydrogenase; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099162:Endothelial PAS Domain-Containing Protein 1; C108095:SDHB protein, human