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

      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; et al. (2007-12-12)
      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.