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

irst mutation that provides an advantage over other cells, allowing them to grow ever-so-slightly faster than their neighbors. But as these driver mutations slowly accumulate in a given cell, the effect is akin to the accelerating growth of savings through compound interest: Increasingly rapid cell division feeds the ever-faster addition of more driver mutations.

Bozic's work hints that the time elapsed between driver mutations in a nascent tumor may be key to ultimate outcomes.

"For instance, we find that an individual who goes 20 years without experiencing a second driver mutation in the same cell might never see the tumor grow to more than a few thousandths of a gram," she says. "But a second driver mutation within five years may develop within 25 years into a tumor weighing hundreds of grams."

These predictions are consistent with clinical observations that it generally takes 30 or more years for human cancers to develop from initiated cells. Bozic and colleagues also verified the accuracy of their model by testing against clinical data from two well-studied tumors, glioblastoma multiforme and pancreatic adenocarcinoma.

In addition to clarifying the advantage bestowed by each driver mutation, Bozic and colleagues provide a formula for estimating the number of these in a given tumor.

"Needless to say, figuring out which mutations, and how many mutations, are drivers of cancer is very important in developing effective therapies," she says. "We hope our work will help drive new lines of research into future treatments."


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Contact: Steve Bradt
steve_bradt@harvard.edu
617-496-8070
Harvard University
Source:Eurekalert

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