Fumarate hydratase deficient uerine fibroids; a distinct gene expression profile

847Defects in enzymes of the mitochondrial tricarboxylic acid (TCA) cycle predispose the individual to severe developmental defects and also to tumorigenesis. Mutations in succinate dehydrogenase (SDH) subunit genes, SDHB, SDHC, and SDHD, cause familial and sporadic pheochromocytoma and paraganglioma, and heterozygous germline mutations in the nuclear gene encoding fumarate hydratase (FH) cause Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). Although recent reports suggest that the stabilization of HIF-1α is often detected in FH and SDH-deficient cells, the mechanisms leading from defects in mitochondrial metabolism to tumorigenesis are still far from being well understood. With an expression microarray approach, we have studied the differences in the global gene expression pattern caused by mutations in FH. We compared 7 uterine fibroids carrying FH mutations to 15 fibroids …