Faculty Collaboration Database

Clonal diversification of primary BALB/c plasmacytomas harboring T(12;15) chromosomal translocations. Leukemia 2000 May;14(5):909-21

Date

05/10/2000

Pubmed ID

10803525

DOI

10.1038/sj.leu.2401676

Scopus ID

2-s2.0-0034055667 (requires institutional sign-in at Scopus site)   18 Citations

Abstract

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.

Author List

Kovalchuk AL, Mushinski EB, Janz S

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Chromosome Mapping
Genes, Immunoglobulin
Genes, myc
Genetic Variation
Immunoglobulin A
Immunoglobulin G
Immunoglobulin Heavy Chains
Mice
Mice, Inbred BALB C
Neoplasm Staging
Plasma Cells
Plasmacytoma
Polymerase Chain Reaction
Translocation, Genetic