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 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.
O'Neil
Jennifer
J
Department of Pediatric Oncology, Belfer Foundation Institute for Innovative Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Tchinda
Joelle
J
Gutierrez
Alejandro
A
Moreau
Lisa
L
Maser
Richard S
RS
Wong
Kwok-Kin
KK
Li
Wei
W
McKenna
Keith
K
Liu
X Shirley
XS
Feng
Bin
B
Neuberg
Donna
D
Silverman
Lewis
L
DeAngelo
Daniel J
DJ
Kutok
Jeffery L
JL
Rothstein
Rodney
R
DePinho
Ronald A
RA
Chin
Lynda
L
Lee
Charles
C
Look
A Thomas
AT
D020087:Alu Elements / Q000235:genetics*; D001483:Base Sequence; D020440:Gene Duplication; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics*; D011995:Recombination, Genetic
D020598:Proto-Oncogene Proteins c-myb