Clonal diversification of primary BALB/c plasmacytomas harboring T(12;15) chromosomal translocations.
DNA sequence analysis of PCR amplified Igh/c-myc junction fragments of T(12;15) chromosome translocations and immunohistochemical determination of immunoglobulin isotype production were employed to study the clonal diversification of neoplastic translocated plasma cells that resided in peritoneal inflammatory granulomas of BALB/c mice harboring primary plasmacytomas. The diversity of plasma cells was found to take two major forms when the fine structure of the T(12;15) translocation was used as the clonotypic marker. First, mosaics of clones containing translocations that were apparently unrelated to each other were detected in nine out of 17 (53%) mice. Second, subclones derived from common T(12;15)+ progenitors by either secondary deletions in translocation breakpoint regions or aberrant isotype switching near translocation breaksites were found in five of 17 (29.5%) mice. When Ig expression was utilized as the clonotypic marker, clonal mosaics were shown to occur in all mice. This was demonstrated by the finding that the prevalent IgA- or IgG-producing plasmacytoma clone was invariably accompanied by smaller clones of IgG- or IgA-expressing neoplastic plasma cells, respectively. These results provided new insights into the clonal diversification at the terminal stage of plasmacytomagenesis. In addition, they suggested that BALB/c plasmacytomas may be uniquely useful for studying clonal diversity during B cell oncogenesis, since clonal evolution can be evaluated in a pool of tumor and tumor precursor cells that is clearly defined by the T(12;15) chromosomal translocation and the production of monoclonal immunoglobulin.
Kovalchuk
A L
AL
Laboratory of Genetics, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.
Mushinski
E B
EB
Janz
S
S
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D005803:Genes, Immunoglobulin; D016259:Genes, myc; D014644:Genetic Variation; D007070:Immunoglobulin A / Q000235:genetics; D007074:Immunoglobulin G / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009367:Neoplasm Staging; D010950:Plasma Cells / Q000473:pathology; D010954:Plasmacytoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016133:Polymerase Chain Reaction; D014178:Translocation, Genetic
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains