Abstract
Genetic rearrangements activating the proto-oncogene c-myc comprise a mandatory oncogenic step in plasma cell tumor development in BALB/cAnPt mice. In the majority of plasmacytomas, c-myc activating rearrangements take the form of reciprocal chromosomal translocations t(12;15) that juxtapose c-myc to the immunoglobulin heavy chain a locus (IgHa) in particular die switch a region (Sα).The genetic basis for the prevalence of Sα/c-myc recombinations in BALB/cAnPt plasmacytomas is not known but may be related to a hypothetical regional genomic instability of the c-myc and IgHα loci in BALB/cAnPt mice. We wished to test whether the genomic instability of both loci might be revealed by the diversity of genetic recombinations that can be observed in IgHα and c-myc. We employed PCR methods to detect new recombinations of c-myc and IgHα in the preneoplastic stage of plasma cell tumor development and found that c-myc can be joined to more genes or genomic regions than known before. This is indicative but does not formally prove a particular genomic instability of c-myc and IgHα in BALB/cAnPt B cells. Since defective DNA repair provides a mechanistic explanation for genomic instability, we measured the efficiency of repair in IgHα and c-myc using an assay that quantitates the removal of UV-induced pyrimidine dimers within specific genomic regions. We used plasmacytoma XRPC 24 as a model system and found that both IgHα and c-myc were poorly repaired, whereas c-abl, a proto-oncogene not related to conventional pristane-induced plasmacytoma-genesis, was efficiently repaired.
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© 1995 Springer-Verlag Berlin Heidelberg
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Janz, S., Jones, G.M., Müller, J.R., Potter, M. (1995). Genomic Instability in B-Cells and Diversity of Recombinations That Activate c-myc. In: Potter, M., Melchers, F. (eds) Mechanisms in B-Cell Neoplasia 1994. Current Topics in Microbiology and Immunology, vol 194. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79275-5_43
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DOI: https://doi.org/10.1007/978-3-642-79275-5_43
Publisher Name: Springer, Berlin, Heidelberg
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