(Press-News.org) 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."
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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.
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Montreal September 28, 2010 – Loners and antisocial kids who reject other children are often bullied at school – an accepted form of punishment from peers as they establish social order. Such peer victimization may be an extreme group response to control renegades, according to a new study from Concordia University published in the Journal of Early Adolescence.
"For groups to survive, they need to keep their members under control," says author William M. Bukowski, a professor at the Concordia Department of Psychology and director of its Centre for Research in Human Development. ...
A new study by University of Notre Dame ecologist Jennifer Tank and colleagues reveals that streams throughout the Midwest are receiving transgenic materials from corn crop byproducts, even six months after harvest.
Transgenic maize (corn) has been genetically engineered to produce its own insecticide, a delta endotoxin from the bacterium Bacillus thuringiensis (Bt). Bt endotoxins deter crop pests, such as the European corn borer.
In a 2007 paper in the Proceedings of the National Academy of Science (PNAS), Tank and a group of researchers demonstrated that transgenic ...
EAST PROVIDENCE, RI – Although research has shown that teens with mental health disorders are more likely to engage in high risk sexual behaviors, like unprotected sex, a new study from the Bradley Hasbro Children's Research Center suggests there is an additional risk associated with certain psychiatric diagnoses.
According to researchers, teens who experience the manic phase of bipolar disorder – which is marked by dramatic mood swings from euphoria and elation to irritability – are more sexually active, have more sexual partners and are more likely to have a sexually ...
While many young adults will share the details of their daily lives with dozens – sometimes hundreds – of friends on Facebook, communicating with their health care providers about mental illness is another story.
"Roughly one in every five young adults between 18 and 25 has a mental illness," says Melissa Pinto-Foltz, a postdoctoral scholar and instructor at the Frances Payne Bolton School of Nursing at Case Western Reserve University. "Seventy percent of them don't receive treatment. Of those that do receive treatment, they have trouble managing the illness and often ...
COLUMBIA, Mo. – University of Missouri researchers believe they have found a critical piece of the puzzle for the treatment of Spinal Muscular Atrophy (SMA) – the leading genetic cause of infantile death in the world. Nearly one in 6,000 births has SMA, and it is estimated that nearly one in 30 to 40 people have the trait that leads to SMA.
In a new study in Human Molecular Genetics, Christian Lorson, professor in the Department of Veterinary Pathobiology and the Department of Molecular Microbiology and Immunology, has found prenatal cardiac defects in mice with SMA. Lorson ...
Montreal September 28, 2010 – Multicultural education in classrooms has failed to produce a deeper understanding across cultures, according to a Concordia University researcher. Education professor Adeela Arshad-Ayaz blames teacher training for failing to address issues of diversity and equity. Her recent presentation at the Congress of the Humanities and Social Sciences, in Montreal, calls for an alternative approach.
"The way we currently teach multiculturalism fails to bring divergent groups together," says Dr. Arshad-Ayaz. "Our present approach is alienating minority ...
CINCINNATI—Firefighters are exposed to potentially dangerous levels of ultrafine particulates at the time they are least likely to wear protective breathing equipment. Because of this, researchers believe firefighters may face an increased risk for heart disease from exposures during the fire suppression process.
Coronary heart disease is the No. 1 killer of American firefighters, with many of these incidents taking place during or just after a firefighting incident. Researchers say exposure to these harmful ultrafine air particulates could predispose firefighters to ...
PHILADELPHIA (September 28, 2010) – Scientists at the Monell Center have used a well-known example of individual differences to identify a genetic contribution to the sense of smell.
Most people detect a distinct sulfurous odor in their urine shortly after eating asparagus. However, there are some who seemingly do not notice the unpleasant odor.
Up until now, it has been unclear whether this is because these individuals do not produce the odor or because they cannot smell it.
Addressing this mystery from several angles, scientists from the Monell Center first used ...
HIV-infected individuals who begin antiretroviral therapy (ART) soon after acquiring the virus may have stronger immune responses to other pathogens than HIV-infected individuals who begin ART later, a new study from the National Institutes of Health has found. This finding suggests that early initiation of ART may prevent irreversible immune system damage and adds to the body of evidence showing significant health benefits from early ART.
Scientists from the National Institute of Allergy and Infectious Diseases, part of NIH, measured the quantity and qualities of B cells ...
Dairy farmers can greatly reduce ammonia emissions from their production facilities by injecting liquid manure into crop fields below the soil surface, according to research by the U.S. Department of Agriculture (USDA).
These findings, which resulted from a study conducted by soil scientist April Leytem and agricultural engineer David Bjorneberg with USDA's Agricultural Research Service (ARS), could help Idaho dairy farmers increase nitrogen capture in the soil and protect air quality from agricultural ammonia emissions. ARS is USDA's principal intramural scientific ...
