51. Functional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma.
- Author
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Gimenez-Roqueplo AP, Favier J, Rustin P, Rieubland C, Kerlan V, Plouin PF, Rötig A, and Jeunemaitre X
- Subjects
- Adrenal Gland Neoplasms enzymology, Basic Helix-Loop-Helix Transcription Factors, Chromosomes, Human, Pair 1, DNA Mutational Analysis, Electron Transport Complex II, Endothelial Growth Factors genetics, Female, Gene Expression, Germ-Line Mutation, Humans, Immunohistochemistry, In Situ Hybridization, Iron-Sulfur Proteins physiology, Loss of Heterozygosity, Lymphokines genetics, Middle Aged, Multienzyme Complexes deficiency, Multienzyme Complexes genetics, Mutation, Missense, Oxidoreductases deficiency, Oxidoreductases genetics, Pheochromocytoma enzymology, Protein Subunits, RNA, Messenger analysis, Sequence Analysis, DNA, Succinate Dehydrogenase deficiency, Succinate Dehydrogenase genetics, Tomography, X-Ray Computed, Trans-Activators genetics, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Adrenal Gland Neoplasms genetics, Iron-Sulfur Proteins genetics, Mutation, Pheochromocytoma genetics
- 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.
- Published
- 2002
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