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Genetic recombinations between c-myc and Igh mu as precursors for recombinations between c-myc and Igh alpha in BALB/c plasmacytomas. Curr Top Microbiol Immunol 1997;224:241-50

Date

01/01/1997

Pubmed ID

9308247

DOI

10.1007/978-3-642-60801-8_24

Scopus ID

2-s2.0-0030753424   2 Citations

Abstract

In this paper we present evidence that primary plasmacytomas harboring a balanced chromosomal translocation t(12;15) may consist of a mosaic of neoplastic clones of tumor cells, in which some of the clones are derived from common progenitors by large additional deletions which alter or "remodel" the fine structure of the t(12;15) on the c-myc-deregulating chromosome. This finding is based on the molecular analysis of the t(12;15) in three plasmacytomas, TEPC 1194, PCT 4127 and PCT 4132, in which primary clones of tumor cells with recombinations between the Ig heavy-chain (Igh) mu locus (Igh mu) and c-myc were found to be related to secondary clones of tumor cells with recombinations between the Igh alpha locus (Igh alpha) and c-myc. Clonal relatedness was based on unique junction fragments between S mu and c-myc that were found to be identical in Igh mu/c-myc and Igh alpha/c-myc breakpoint regions. S mu/c-myc breakpoints with adjoining sequences can thus be used as clonotypic markers, providing molecular fingerprints for the evolution of precursor cells with Igh mu/c-myc recombinations into progenitor cells with Igh alpha/c-myc recombinations. We propose that aberrant isotype switch recombination or illegitimate rearrangement in switch regions converts Igh mu/c-myc rearrangements, which are found very rarely in established plasmacytomas, into Igh alpha/c-myc rearrangements, which are present in about 80% of plasmacytomas with t(12;15). Remodeling of the t(12;15) results in closer juxtaposition of c-myc to the 3'-C alpha locus control region and probably in enhanced transcription of c-myc. We suggest that remodeling of c-myc-deregulating rearrangements constitutes a novel progression mechanism in malignant B-cell development.

Author List

Janz S, Kovalchuk AL, Müller JR, Potter M

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
DNA, Neoplasm
Gene Rearrangement, B-Lymphocyte, Heavy Chain
Genes, Immunoglobulin
Genes, myc
Mice
Mice, Inbred BALB C
Models, Biological
Molecular Sequence Data
Plasmacytoma
Polymerase Chain Reaction
Recombination, Genetic
Translocation, Genetic