Fueling Tumor Growth

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Science  08 Mar 2002:
Vol. 295, Issue 5561, pp. 1795
DOI: 10.1126/science.295.5561.1795d

Uterine leiomyomata, or “fibroids,” are smooth muscle tumors that affect a substantial proportion of the female population. Although benign, uterine fibroids can cause excessive bleeding and impair fertility, and they account for about 40% of the 600,000 hysterectomies performed each year in the United States.

An important clue to the molecular pathogenesis of these tumors is provided by the Multiple Leiomyoma Consortium, who have studied families with a rare inherited disorder in which affected females develop fibroids in the skin and uterus at a young age. The consortium traced the disease-causing mutations to the FH gene at chromosome 1q42.3-q43, which encodes the mitochondrial enzyme fumarate hydratase. As part of the tricarboxylic acid (TCA) cycle, fumarate hydratase functions in a fundamental metabolic pathway that provides energy to all cells in the body, and it is the second enzyme (after succinate dehydrogenase) in this pathway that has been classified as a tumor suppressor. Future investigation of the mechanism by which FH mutations disrupt cell growth control may provide new leads for the prevention and treatment of the more common forms of uterine fibroids. — PAK

Nature Genet., 10.1038/ng849 (2002).

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