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.
People who suffer from mental health issues also suffer from its stigma. Portraying mental illness as a good thing helps no one
The inventor of a breakthrough DNA test for Down syndrome says the technology can be used to screen people for cancer.The Hong Kong scientist who invented a simple blood test to show pregnant women if their babies have Down syndrome is now testing a similar technology for cancer.
Dr Jeremy Farrar of Wellcome Trust says international community is belatedly taking actions necessary to stem tide of disease
Miniature stomachs gastric organoids will help in study of ulcers and could be used in future to repair patients stomachs
The story of the vaccines development is just one part of a rich and intertwined history of scientific discovery and controversy
A highly sensitive blood test for Ebola exists, so why isn't it being used to test all returning health workers from West Africa? Because the virus isn't in the blood in the first stages of infection.
Drinking beverages enriched with compounds found in cocoa beans improved older adults' performances on a memory test – but there's a catch
A 700-year-old caribou dropping from northern Canada holds surprisingly well-preserved viruses. There's no evidence the viruses are dangerous, but they are scientifically interesting.
The New England Journal of Medicine published an editorial against quarantining people who have worked with Ebola patients in Africa. Renee Montagne speaks with Dr. Lindsey Baden, one of the authors.
Surgeons in Australia say they have performed the first heart transplant using a "dead heart".