Alu elements mediate MYB gene tandem duplication in human T-ALL
Department of Pediatric Oncology; Department of Molecular Genetics and Microbiology
Medical Subject Headings
Alu Elements; Base Sequence; *Gene Duplication; Humans; In Situ Hybridization, Fluorescence; Leukemia-Lymphoma, Adult T-Cell; Models, Biological; Models, Genetic; Molecular Sequence Data; Nucleic Acid Hybridization; Polymerase Chain Reaction; Proto-Oncogene Proteins c-myb; Recombination, Genetic
Life Sciences | Medicine and Health Sciences
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 approximately 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.
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Citation: J Exp Med. 2007 Dec 24;204(13):3059-66. Epub 2007 Dec 10. Link to article on publisher's site
The Journal of experimental medicine
O'Neil, Jennifer Elinor; Tchinda, Joelle; Gutierrez, Alejandro; Moreau, Lisa A.; Maser, Richard S.; Wong, Kwok-Kin; Li, Wei; McKenna, Keith; Liu, X. Shirley; Feng, Bin; Neuberg, Donna S.; Silverman, Lewis B.; DeAngelo, Daniel J.; Kutok, Jeffery L.; Rothstein, Rodney; DePinho, Ronald A.; Chin, Lynda; Lee, Charles; and Look, A. Thomas, "Alu elements mediate MYB gene tandem duplication in human T-ALL" (2007). GSBS Student Publications. 1420.