title: Genetic reporter system for oncogenic Igh-Myc translocations in mice.
abstract: The Myc-deregulating chromosomal T(12;15)(Igh-Myc) translocation, the hallmark mutation of inflammation- and interleukin 6-dependent mouse plasmacytoma (PCT), is the premier model of cancer-associated chromosomal translocations because it is the only translocation in mice that occurs spontaneously (B lymphocyte lineage) and with predictably high incidence (approximately 85% of PCT), and has a direct counterpart in humans: Burkitt lymphoma t(8;14)(q24;q32) translocation. Here, we report on the development of a genetic system for the detection of T(12;15)(Igh-Myc) translocations in plasma cells of a mouse strain in which an enhanced green fluorescent protein (GFP)-encoding reporter gene has been targeted to Myc. Four of the PCTs that developed in the newly generated translocation reporter mice, designated iGFP(5'Myc), expressed GFP consequent to naturally occurring T(12;15) translocation. GFP expression did not interfere with tumor development or the deregulation of Myc on derivative 12 of translocation, der (12), because the reporter gene was allocated to the reciprocal product of translocation, der (15). Although the described reporter gene approach requires refinement before T(12;15) translocations can be quantitatively detected in vivo, including in B lymphocyte lineage cells that have not yet completed malignant transformation, our findings provide proof of principle that reporter gene tagging of oncogenes in gene-targeted mice can be used to elucidate unresolved questions on the occurrence, distribution and trafficking of cells that have acquired cancer-causing chromosomal translocations of great relevance for humans.
authors.affiliation: Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Takizawa
authors.forename: J S
authors.initials: JS
authors.lastname: Kim
authors.forename: L
authors.initials: L
authors.lastname: Tessarollo
authors.forename: N
authors.initials: N
authors.lastname: McNeil
authors.forename: T J
authors.initials: TJ
authors.lastname: Waldschmidt
authors.forename: R
authors.initials: R
authors.lastname: Casellas
authors.forename: T
authors.initials: T
authors.lastname: Ried
authors.forename: S
authors.initials: S
authors.lastname: Janz
mesh_terms: D000818:Animals; D017930:Genes, Reporter; D016259:Genes, myc; D049452:Green Fluorescent Proteins / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: D007143:Immunoglobulin Heavy Chains; D049452:Green Fluorescent Proteins
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