As anyone familiar with the X-Men knows, mutants can be either very good or very bad — or somewhere in between. The same appears true within cancer cells, which may harbor hundreds of mutations that set them apart from other cells in the body; the scientific challenge has been to figure out which mutations are culprits and which are innocent bystanders. Now, researchers at Johns Hopkins Medicine have devised a novel approach to sorting them out: they generated random mutations in a gene associated with lymphoma, tested the proteins produced by the genes to see how they performed, and generated a catalog of mutants with cancer-causing potential.
"Our goal was to correlate various mutations with potential to promote lymphoma," says Joel Pomerantz, Ph.D., an associate professor in the Johns Hopkins School of Medicine's Institute for Cell Engineering. For the study, to be reported in a January 2013 issue of Molecular and Cellular Biology, Pomerantz and his research team focused on the protein CARD11. CARD11 plays a key role in signaling the presence of infection, which leads infection-fighting white blood cells to grow and divide. Certain mutations can turn CARD11 permanently "on," causing out-of-control cell division that results in cancers called lymphomas, which strike about 75,000 Americans each year.
To find out which genetic mutations would increase CARD11's activity, Pomerantz and his team made copies of the CARD11 gene in a way that made random mutations likely. They then used the faulty copies to make mutant proteins, and tested the ability of those proteins to trigger the signaling reaction that is CARD11's specialty. This let the researchers figure out which mutations increased the protein's activity, and by how much — information that can be compared to emerging data about CARD11 mutations found in human lymphomas. "We found that several of the overactive mutations we'd identified have already been found in patients," Pomerantz says.
Noting that CARD11 is part of the NF-κB signaling pathway, a target of some cancer therapies, Pomerantz says the new cataloging technique could lead to more personalized treatment. "We imagine eventually being able to correlate response to a particular therapy with a particular mutation," he says. For now, Pomerantz and his team are delving deeper into what gives the bad CARD11 mutants their special powers, looking for mechanisms to explain how certain changes increase the protein's activity.
Johns Hopkins Medicine: http://www.hopkinsmedicine.org
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Genetic study could provide hope for men with advanced forms of the disease with findings that could lead to personalised treatments
The agency that administers Obamacare in California moved to make expensive medicines more affordable in 2016. In most plans, patients will pay no more than $150 or $250 a month.
When former prisoners flock together, more land back in jail
Avian influenza is ravaging poultry flocks across the Upper Midwest. The virus is "doing things we've never seen it do before," and understanding about transmission is very limited, a scientist says.
Youthful blood has once again shown its promise as an elixir of youth – this time helping to rejuvenate bones. But exactly how it does so is still to be unravelled
LONDON (Reuters) - Victims of childhood bullying are more likely to be overweight or obese as adults and have a higher risk of developing heart disease, diabetes and other illnesses, according to a study by British psychiatrists.
Study finds nixing phones is equivalent to adding an hour of learning to the school week, or five days to the school year
Drug-resistant tuberculosis is a growing problem. It's spread through the air. It can kill you. And it's incredibly difficult to treat. But a program in Peru shows that the disease can be cured.
Scientists have diagnosed strain of leprosy on man from Scandinavia who died in Essex in the fifth or early sixth century
Legalization keeps rolling ahead. But because of years of government roadblocks on research, we don’t know nearly enough about the dangers of marijuana—or the benefits