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

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 Al...

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Detalles Bibliográficos
Autores principales: O'Neil, Jennifer, Tchinda, Joelle, Gutierrez, Alejandro, Moreau, Lisa, Maser, Richard S., Wong, Kwok-Kin, Li, Wei, McKenna, Keith, Liu, X. Shirley, Feng, Bin, Neuberg, Donna, Silverman, Lewis, DeAngelo, Daniel J., Kutok, Jeffery L., Rothstein, Rodney, DePinho, Ronald A., Chin, Lynda, Lee, Charles, Look, A. Thomas
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Brief Definitive Reports
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150982/
https://www.ncbi.nlm.nih.gov/pubmed/18070937
http://dx.doi.org/10.1084/jem.20071637
Descripción
Sumario: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.

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