Navigation Links
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 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
steve_bradt@harvard.edu
617-496-8070
Harvard University
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:9/20/2017)... NC (PRWEB) , ... September 20, 2017 , ... ... Transformation and Centers of Excellence (CoE) with the latest Artificial Intelligence (AI) thinking, ... designed presence offers quick and easy access to essential information that offers a ...
(Date:9/20/2017)... GLENDALE, Calif. (PRWEB) , ... September 20, 2017 ... ... 15th year of providing a voice for people who have kidney disease. The ... many writers to share their stories. Entrants needed to meet only one ...
(Date:9/20/2017)... ... 2017 , ... Mirror Mirror Beauty Boutique is excited to ... Autumn with CoolSculpting®. Scheduled for Thursday, September 28th, the afternoon will include live ... Boutique is Houston’s largest CoolSculpting provider, holding the prestigious title of ...
(Date:9/20/2017)... ... 20, 2017 , ... As part of The Garland Company, ... redesigned website. The new site – still located at http://www.garlandco.com – ... other industry users that Garland serves. , After an ambitious phase of industry ...
(Date:9/20/2017)... ... September 20, 2017 , ... In just a short time since going ... receiving positive feedback from customers trying the product for the first time, and others ... was developed by neurosurgeon Shawn Moore, MD, for everyone from athletes at risk from ...
Breaking Medicine News(10 mins):
(Date:9/6/2017)... Sept. 6, 2017  Medical professionals are ... skills while treating their patients. Medical simulations ... without involving patients. Simulation provides a safe ... carry out procedures, refine techniques and build ... of new technology, such as augmented reality, ...
(Date:9/5/2017)... Sapheneia and Scannerside received FDA 510(k) clearance ... a third-party Vendor neutral CT product that makes it ... with current MITA standards. ... is specifically designed to provide CT operators, prior to ... over a predefined threshold. Scannerside Dose Check is intended ...
(Date:9/5/2017)... -- Oramed Pharmaceuticals Inc. (NASDAQ: ORMP ) ... focused on the development of oral drug delivery systems, ... with the U.S. Food and Drug Administration (FDA) regarding ... At the meeting, the FDA ... of ORMD-0801, would be a Biologics License Application (BLA).  ...
Breaking Medicine Technology: