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.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenal Gland Neoplasms / enzymology
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Adrenal Gland Neoplasms / genetics*
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Basic Helix-Loop-Helix Transcription Factors
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Chromosomes, Human, Pair 1
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DNA Mutational Analysis
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Electron Transport Complex II
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Endothelial Growth Factors / genetics
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Female
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Gene Expression
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Germ-Line Mutation
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Humans
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Immunohistochemistry
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In Situ Hybridization
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Iron-Sulfur Proteins / genetics*
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Iron-Sulfur Proteins / physiology
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Loss of Heterozygosity
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Lymphokines / genetics
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Middle Aged
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Multienzyme Complexes / deficiency
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Multienzyme Complexes / genetics
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Mutation*
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Mutation, Missense
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Oxidoreductases / deficiency
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Oxidoreductases / genetics
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Pheochromocytoma / enzymology
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Pheochromocytoma / genetics*
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Protein Subunits
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RNA, Messenger / analysis
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Sequence Analysis, DNA
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Succinate Dehydrogenase / deficiency
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Succinate Dehydrogenase / genetics
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Tomography, X-Ray Computed
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Trans-Activators / genetics
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Endothelial Growth Factors
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Iron-Sulfur Proteins
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Lymphokines
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Multienzyme Complexes
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Protein Subunits
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RNA, Messenger
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Trans-Activators
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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endothelial PAS domain-containing protein 1
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Oxidoreductases
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Electron Transport Complex II
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SDHB protein, human
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Succinate Dehydrogenase