A new study by scientists from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), part of the National Institutes of Health, resolves longstanding questions about the origin of recurrent chromosomal rearrangements — known as translocations — that drive lymphomas and leukemias in humans.
In the new study, NIAMS scientists used cutting-edge technologies to explore the three theories. Using immune cells known as B cells, they found that the frequency of DNA damage was directly proportional to the frequency of translocation. Intriguingly, the researchers found that an enzyme, called AID, damages approximately 150 genes in the B cell genome, thus making them susceptible to translocations. Among the targeted genes, many have been previously shown to be translocated in human cancer. Further study also revealed that, in the absence of AID, gene proximity or interaction frequency was the driving force behind translocations. The new results not only clarify the origin of tumor-inducing translocations, but they also suggest that finding ways to stop AID could potentially prevent the development of many human cancers. This work was also supported by the NIH’s National Cancer Institute (NCI) and other organizations.
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Article: |
Ofir Hakim et al. DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes. Nature DOI: 10.1038/nature10909. [Epub ahead of print]
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Who: |
Rafael Casellas, Ph.D., Chief, Genomics and Immunity Section, NIAMS, and Adjunct Investigator, NCI, is available to comment on the study.
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Contact: |
To schedule interviews, please contact Trish Reynolds at (301) 496-8190 or [email protected]. |
The mission of the NIAMS, a part of the U.S. Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about the NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at http://www.niams.nih.gov.