Isotype switch-mediated CH deletions are a recurrent feature of Myc/CH translocations in peritoneal plasmacytomas in mice.
Oncogene activating chromosomal translocations that interrupt IGH switch (S) regions at 14q32 are thought to be caused by misguided IGH isotype switching in postgerminal center B-cell lymphomas and plasma cell myelomas in humans. Aberrant switching also seems to be involved in altering the fine structure of the translocation in some of these tumors, but the significance of these changes is not known. Here we report on 3 cases of IL-6 transgenic mouse plasmacytomas (PCT) that harbor T(12;15) translocations that had been modified by frustrated switch attempts that result in C(H) deletions. When considered together with 6 similar cases of PCT described previously, our observations suggest that secondary deletions in C(H) are a regular feature in the molecular evolution of T(12;15) translocations and, thereby, in the progression of PCT. We propose that the T(12;15)(+) mouse PCT offers a uniquely valuable model system for elucidating the dual role of abnormal isotype switching in causation and 'remodeling' of chromosomal translocations.
Kovalchuk
Alexander L
AL
Laboratory of Genetics, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Janz
Siegfried
S
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D016259:Genes, myc; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007132:Immunoglobulin Isotypes / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology; D010954:Plasmacytoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D017384:Sequence Deletion; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D015850:Interleukin-6