Uncoupling of genomic instability and tumorigenesis in a mouse model of Burkitt's lymphoma expressing a conditional box II-deleted Myc protein.
Burkitt's lymphomas (BL) are characterized by the constitutive expression of c-Myc protein. In total, 50-60% of all BL cells carry mutant c-Myc proteins. Using a mouse model of spontaneously immortalized pro-B-lymphocytes (Ba/F3), we have investigated genomic instability mediated by the conditional expression of either wild-type (WT) or deletion box II Delta106-Myc proteins. We found that both proteins mediate common as well as differing types of chromosomal rearrangements as documented by spectral karyotyping (SKY). A higher level of genomic instability is induced by the Delta106-Myc protein. To examine the tumorigenic potential of WT or Delta106-driven Ba/F3 cells, in vivo tumorigenesis studies were performed in SCID mice. Under the experimental conditions of this study, WT but not Delta106-Myc expressing Ba/F3 cells triggered tumorigenesis in SCID mice. Therefore, the genomic instability phenotype induced by Delta106-Myc can be genetically uncoupled from its tumorigenic potential.
Fest
Thierry
T
Manitoba Institute of Cell Biology and The Genomic Center for Cancer Research and Diagnosis, The University of Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada.
Guffei
Amanda
A
Williams
Gaynor
G
Silva
Santiago
S
Mai
Sabine
S
D000818:Animals; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D002875:Chromosomes; D004195:Disease Models, Animal; D042822:Genomic Instability; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion
C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc