Journal article
Plasma cell tumour progression in iMycEmu gene-insertion mice
The Journal of pathology, Vol.209(1), pp.44-55
05/2006
DOI: 10.1002/path.1940
PMID: 16482495
Abstract
The authors have recently reported that gene-targeted iMyc(Emu) mice that carry a His(6)-tagged mouse Myc cDNA, Myc(His), just 5' of the immunoglobulin heavy-chain enhancer, Emu, are prone to 'spontaneous' neoplasms of the B-lymphocyte lineage. The present study has used histological, immunohistochemical, and molecular genetic methods to investigate a subset of these neoplasms referred to as extraosseous plasmacytomas (PCTs). It is shown that 20.8% (20/96) of tumour-bearing iMyc(Emu) mice on a mixed genetic background of segregating C57BL/6 and 129/SvJ alleles develop PCT by 500 days. The Myc(His)-induced PCTs produced monoclonal immunoglobulin and developed in the gut-associated lymphoid tissue (GALT), particularly the mesenteric node and Peyer's patches. The PCTs overexpressed Myc(His), at the expense of normal Myc, and exhibited gene expression changes on cDNA macroarrays that were consistent with Myc(His)-driven neoplasia. Surprisingly, in one of three PCT-derived cell lines, Myc(His) was 'replaced' by a naturally occurring T(12;15) translocation, which changed the mode of Myc deregulation from gene insertion (Myc(His) transgene) to chromosomal translocation (juxtaposition of normal Myc to the immunoglobulin heavy-chain locus Igh). These findings provide evidence that recreation of the mouse PCT-associated T(12;15)(Igh(Emu)-Myc) translocation by gene insertion in mice results in the predictable development of PCTs in approximately one-fifth of the tumour-bearing mice. Myc(His)-driven PCTs recapitulate aspects of human plasma cell neoplasms, for which relatively few models exist in mice. For example, PCT development in the iMyc(Emu) mice may provide a good system to study the mechanism by which human MYC facilitates the progression of plasma cell myeloma (multiple myeloma) in humans.
Details
- Title: Subtitle
- Plasma cell tumour progression in iMycEmu gene-insertion mice
- Creators
- J S Kim - Laboratory of Genetics, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USAS S HanS S ParkN McNeilS Janz
- Resource Type
- Journal article
- Publication Details
- The Journal of pathology, Vol.209(1), pp.44-55
- DOI
- 10.1002/path.1940
- PMID
- 16482495
- ISSN
- 0022-3417
- eISSN
- 1096-9896
- Language
- English
- Date published
- 05/2006
- Academic Unit
- Stead Family Department of Pediatrics; Pathology
- Record Identifier
- 9984083219802771
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