Technique Catalogs Lymphoma-Linked Genetic Variations

A novel approach has been devised to sort out random mutations in genes associated with lymphoma, and the proteins produced by the genes could be tested to see how they performed.

Antigen receptor signaling to nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB), is essential for normal lymphocyte activation, but is dysregulated in several types of lymphoma.

Scientists at Johns Hopkins School of Medicine (Baltimore, MD, USA) made copies of the caspase recruitment domain family, member 11 (CARD11) gene in a way that made random mutations likely. The CARD11 protein plays a key role in signaling the presence of infection, which leads infection-fighting white blood cells to grow and divide.

The investigators 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 allowed them to find to which mutations increased the protein's activity and by how much and this information could then be compared to emerging data about CARD11 mutations found in human lymphomas. They noted that CARD11 is part of the NF- κB signaling pathway, a target of some cancer therapies
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Joel Pomerantz, PhD, an associate professor in the Johns Hopkins School of Medicine's Institute for Cell Engineering, and senior author of the study said "Our goal was to correlate various mutations with potential to promote lymphoma. We imagine eventually being able to correlate response to a particular therapy with a particular mutation." The cancers called lymphomas, affect about 75,000 patients in the United States of America each year. The study was published in the January 2013 issue of the journal Molecular and Cellular Biology.

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