The Journal of Experimental Medicine
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Published online December 10, 2007
doi:10.1084/jem.20071637
The Journal of Experimental Medicine, Vol. 204, No. 13, 3059-3066
The Rockefeller University Press, 0022-1007 $30.00
© 2007 O'Neil et al.
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BRIEF DEFINITIVE REPORT

 Alu elements mediate MYB gene tandem duplication in human T-ALL

Jennifer O'Neil1, Joelle Tchinda5, Alejandro Gutierrez1,6, Lisa Moreau1, Richard S. Maser2,7, Kwok-Kin Wong2, Wei Li3,9, Keith McKenna1, X. Shirley Liu3,9, Bin Feng4, Donna Neuberg3,9, Lewis Silverman1, Daniel J. DeAngelo2, Jeffery L. Kutok5, Rodney Rothstein10, Ronald A. DePinho2,4,7, Lynda Chin2,4,8, Charles Lee5, and A. Thomas Look1,6

1 Department of Pediatric Oncology, 2 Department of Medical Oncology, 3 Department of Biostatistics and Computational Biology, and 4 Center for Applied Cancer Science, Belfer Foundation Institute for Innovative Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02115
5 Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115
6 Division of Hematology, Children's Hospital Boston, Boston, MA 02115
7 Department of Genetics and Medicine and 8 Department of Dermatology, Harvard Medical School, Boston, MA 02115
9 Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115
10 Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032

CORRESPONDENCE A. Thomas Look: Thomas_Look{at}dfci.harvard.edu OR Charles Lee: clee{at}rics.bwh.harvard.edu

Recent studies have demonstrated that the MYB oncogene is frequently duplicated in human T cell acute lymphoblastic leukemia (T-ALL). We find that the human MYB locus is flanked by 257-bp Alu repeats and that the duplication is mediated somatically by homologous recombination between the flanking Alu elements on sister chromatids. Nested long-range PCR analysis indicated a low frequency of homologous recombination leading to MYB tandem duplication in the peripheral blood mononuclear cells of ~50% of healthy individuals, none of whom had a MYB duplication in the germline. We conclude that Alu-mediated MYB tandem duplication occurs at low frequency during normal thymocyte development and is clonally selected during the molecular pathogenesis of human T-ALL.

J. O'Neil and J. Tchinda and C. Lee and A.T. Look contributed equally to this paper.


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