Featured Research

from universities, journals, and other organizations

Individual mutations are very slow to promote tumor growth, mathematical modeling shows

Date:
October 3, 2010
Source:
Harvard University
Summary:
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. The research reinforces that cancer is the culmination of many accumulated mutations, and highlights the fundamental heterogeneity and randomness of many cancers.

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.

Related Articles


Their research, appearing 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 first 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."

Bozic's co-authors on the current PNAS paper are Tibor Antal and Martin A. Nowak of Harvard's Program for Evolutionary Dynamics; Hannah Carter, Dewey Kim, Rachel Karchin, Kenneth W. Kinzler, and Bert Vogelstein of Johns Hopkins University; Hisashi Ohtsuki of the Tokyo Institute of Technology; and Sining Chen of the University of Medicine and Dentistry of New Jersey. Their work was sponsored by the John Templeton Foundation, the National Science Foundation, the National Institutes of Health, the Bill and Melinda Gates Foundation, and J. Epstein.


Story Source:

The above story is based on materials provided by Harvard University. Note: Materials may be edited for content and length.


Journal Reference:

  1. I. Bozic, T. Antal, H. Ohtsuki, H. Carter, D. Kim, S. Chen, R. Karchin, K. W. Kinzler, B. Vogelstein, M. A. Nowak. Accumulation of driver and passenger mutations during tumor progression. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.1010978107

Cite This Page:

Harvard University. "Individual mutations are very slow to promote tumor growth, mathematical modeling shows." ScienceDaily. ScienceDaily, 3 October 2010. <www.sciencedaily.com/releases/2010/09/100928111124.htm>.
Harvard University. (2010, October 3). Individual mutations are very slow to promote tumor growth, mathematical modeling shows. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2010/09/100928111124.htm
Harvard University. "Individual mutations are very slow to promote tumor growth, mathematical modeling shows." ScienceDaily. www.sciencedaily.com/releases/2010/09/100928111124.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Touch-Free Smart Phone Empowers Mobility-Impaired

Touch-Free Smart Phone Empowers Mobility-Impaired

Reuters - Innovations Video Online (Dec. 21, 2014) A touch-free phone developed in Israel enables the mobility-impaired to operate smart phones with just a movement of the head. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Earthworms Provide Cancer-Fighting Bacteria

Earthworms Provide Cancer-Fighting Bacteria

Reuters - Innovations Video Online (Dec. 21, 2014) Polish scientists isolate bacteria from earthworm intestines which they say may be used in antibiotics and cancer treatments. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Existing Chemical Compounds Could Revive Failing Antibiotics, Says Danish Scientist

Existing Chemical Compounds Could Revive Failing Antibiotics, Says Danish Scientist

Reuters - Innovations Video Online (Dec. 21, 2014) A team of scientists led by Danish chemist Jorn Christensen says they have isolated two chemical compounds within an existing antipsychotic medication that could be used to help a range of failing antibiotics work against killer bacterial infections, such as Tuberculosis. Jim Drury went to meet him. Video provided by Reuters
Powered by NewsLook.com
Hugging It Out Could Help You Ward Off A Cold

Hugging It Out Could Help You Ward Off A Cold

Newsy (Dec. 21, 2014) Carnegie Mellon researchers found frequent hugs can help people avoid stress-related illnesses. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins