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Individual mutations are very slow to promote tumor growth
Date:9/28/2010

CAMBRIDGE, Mass., Sept. 28, 2010 -- Individual cancer-causing mutations have a minute effect on tumor growth, increasing the rate of cell division by just 0.4 percent on average, according to new mathematical modeling by scientists at Harvard University, Johns Hopkins University, and other institutions.

Their research, appearing this week in the Proceedings of the National Academy of Sciences, reinforces that cancer is the culmination of many accumulated mutations. It also highlights the fundamental heterogeneity and randomness of many cancers, consistent with the observations of epidemiologists and clinicians.

"This work suggests that significant tumor growth probably requires the slow and steady accumulation of multiple mutations in a cell over a number of years," says lead author Ivana Bozic, a doctoral student in Harvard's Department of Mathematics and Program for Evolutionary Dynamics. "It also helps explain why so many cancer-driving mutations are needed to form an advanced malignancy within the lifetime of an individual."

All of our cells undergo regular division and death, processes that ordinarily balance out each other. In cancer this balance is broken, leading to invasive tumors that crowd out healthy cells and spread in the body.

"While emerging data from the sequencing of cancer genomes are illuminating, their reconciliation with epidemiological and clinical observations poses a major challenge," Bozic says. "Our novel mathematical model begins to address this disconnect."

Bozic's work adds to scientists' recent efforts to differentiate between "driver" and "passenger" mutations in tumors. Researchers have found that most solid tumors contain 40 to 100 mutations in coding genes, but that on average only 5 to 15 of these actually drive tumor growth. The remainder are simply along for the ride: associated with driver mutations, but not benefiting the tumor.

Tumors begin growing with the f
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Contact: Steve Bradt
steve_bradt@harvard.edu
617-496-8070
Harvard University
Source:Eurekalert

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