Navigation Links
Individual mutations are very slow to promote tumor growth

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 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."


Contact: Steve Bradt
Harvard University

Related medicine news :

1. Bacteria identified that may lead to inflammatory bowel disease in certain individuals
2. For migrant workers, community cooperation builds on individual strengths
3. Lung cancer survival rates improved through use of individualized chemotherapy
4. Rectal cancer rates are rising in young individuals
5. Children have a negative impact on physical activity among individuals with heart disease
6. Individuals confess alcohol abuse to clergy
7. Brain responses of obese individuals are more weakly linked to feelings of hunger
8. New research shows peer drug use may increase an individuals genetic tendency to use drugs
9. Molecular Signatures in Post-Mortem Brain Tissue of Younger Individuals at High Risk for Alzheimer's Disease
10. Educate individuals to prevent sky-rocketing health care costs
11. Tai Sophia Institute Offers Individual Graduate-Level Courses
Post Your Comments:
(Date:12/1/2015)... Angeles, CA (PRWEB) , ... December 01, 2015 , ... ... coalition of obesity groups has filed a discrimination claim against the U.S. Department of ... coverage in their Affordable Care Act (ACA) plans are breaking the clause in the ...
(Date:12/1/2015)... Fla. (PRWEB) , ... December 01, 2015 , ... ... number of leadless pacemakers in the U.S. and is the only hospital in ... from the largest clinical data presentation of transcatheter pacing patients were revealed recently ...
(Date:12/1/2015)... Houston, TX (PRWEB) , ... December 01, 2015 , ... ... owner of Vitenas Cosmetic Surgery, has been named by MedEsthetics magazine as the Best ... best of the best among the many elite aesthetic physicians honored by the industry ...
(Date:12/1/2015)... ... 2015 , ... Growth in medical payments per workers’ compensation claim in Louisiana ... and nonhospital care, according to a recent study by the Workers Compensation Research Institute ... found medical payments per claim with more than seven days of lost time continued ...
(Date:12/1/2015)... York, NY (PRWEB) , ... December 01, 2015 ... ... epidemic in the 1980s we have seen vast improvements in scientific research and ... made significant strides, providing increased hope and relief to those affected by HIV/AIDS. ...
Breaking Medicine News(10 mins):
(Date:12/1/2015)... Va. , Dec. 1, 2015  AccuTEC ... unveiled a new corporate logo and brand identity ... the design and engineering of bladed products where ... --> --> Serving manufacturers ... glass, and auto glass equipment, AccuTEC,s product lines ...
(Date:12/1/2015)... , Dec. 1, 2015 During the ... San Francisco, CA , Medinol ... the coronary marketplace. During a satellite symposium, "The ... Design to Minimize Restenosis", a renowned physician panel ... Medinol NIRxcell™ CoCr Coronary Stent System and the ...
(Date:12/1/2015)... ) has ... and Disposables Market by product, by Animal - ... offering. --> ) has announced ... Disposables Market by product, by Animal - Global ... --> Research and Markets ( ...
Breaking Medicine Technology: