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Mutations in different cells cooperate to set the stage for cancer
Date:1/13/2010

According to modern biology textbooks, a single genetic mutation is rarely enough to cause cancer. It is generally thought that cells must accumulate a series of mutations that work together to trigger tumor development. Now, Howard Hughes Medical Institute (HHMI) researchers have shown that distinct cancer-causing mutations in neighboring cells can cooperate to produce tumors.

Cancer biologists have long known that it takes the cooperation of multiple cancer-causing genes - or oncogenes -- to cause cancer. "It was assumed that these mutations have to occur in the same cells to drive tumorigenesis," said HHMI researcher Tian Xu at Yale University. "We have now discovered that the oncogenic mutations don't have to be in the same cells to drive development of cancer. Distinctive mutations occurring in different neighboring cells could cooperate to promote tumorigenesis."

Xu, graduate student Ming Wu, and postdoctoral researcher Jos Carlos Pastor-Pareja, both of whom work in Xu's lab at Yale University, are coauthors of the study published in Nature on January 13, 2010. The findings may open up a new avenue of research into the molecular origins of cancer. They also help to clarify how ordinary cellular stresses, such as wounds or inflammation, may promote cancer development.

Xu's team set out to study the interaction of two mutant genes often detected together in tumors. One of these, RasV12, is a growth-promoter. Ras mutations are well known for their ability to cooperate with other mutations to cause cancer. On its own, however, RasV12 causes only a mild overgrowth of cells. The other gene, scrib-, a non-functioning mutant of a tumor-suppressor gene known as scrib, by itself causes cells to die. When the two mutant genes are found in single cell, they cooperate to produce tumors.

Xu and his colleagues were curious about what would happen when
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Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
Source:Eurekalert

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