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University of Pittsburgh researchers uncover mitochondrial defect involved with inherited cancers

PITTSBURGH, Feb. 3 -- University of Pittsburgh researchers have uncovered a major new concept of how a certain type of tumor develops by linking a specific defect in mitochondria to a type of inherited tumor.

The Pitt scientists, led by Bora E. Baysal, M.D., Ph.D. and Bernie Devlin, Ph.D., department of psychiatry, found that a defective gene on chromosome 11q23, a region previously implicated in the progression of many solid cancerous tumors, causes a hereditary tumor called hereditary paraganglioma. Paraganglioma tumors most commonly occur in the carotid body, a small organ located in the carotid artery in the neck that senses blood oxygen levels. This discovery is important because for the first time it ties a genetic defect in mitochondria (energy producing organelles inside the cell) to tumor development.

Results of the study appear in today's issue of the journal Science.

The researchers became interested in families with paraganglioma who show a peculiar inheritance pattern, which can be explained by a process called "genomic imprinting." While the genetic defect is transmitted through both mothers and fathers, tumors develop only when fathers transmit the defect. The researchers found that a gene named succinate-ubiquinone oxido-reductase (SDHD), that codes for an integral part of mitochondrial complex II, was defective in families with paraganglioma. By the researchers' reasoning, the defect is likely to cause mitochondria to fail to properly sense the oxygen levels in the cell. And, because of the oxygen-sensing defect, the carotid body is chronically stimulated to compensate for the lack of oxygen. This chronic stimulation eventually leads to cellular proliferation and tumor development. Chronic atmospheric hypoxia (reduced oxygen level) was previously linked to the development of paraganglioma tumors in people living at high altitud es.

It is conceivable, argue the researchers, that defect
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Contact: Craig Dunhoff
dunhoffcc@msx.upmc.edu
412-624-2607
University of Pittsburgh Medical Center
2-Feb-2000


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