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Genomic instability in B-cells and diversity of recombinations that activate c-myc. Curr Top Microbiol Immunol 1995;194:373-80

Date

01/01/1995

Pubmed ID

7895512

DOI

10.1007/978-3-642-79275-5_43

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 alpha locus (IgH alpha) in particular the switch alpha region (S alpha). The genetic basis for the prevalence of S alpha/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 IgH alpha 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 IgH alpha and c-myc. We employed PCR methods to detect new recombinations of c-myc and IgH alpha 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 IgH alpha in BALB/cAnPt B cells. Since defective DNA repair provides a mechanistic explanation for genomic instability, we measured the efficiency of repair in IgH alpha 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 IgH alpha and c-myc were poorly repaired, whereas c-abl, a proto-oncogene not related to conventional pristane-induced plasmacytoma-genesis, was efficiently repaired.

Author List

Janz S, Jones GM, 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
B-Lymphocytes
DNA Repair
DNA, Neoplasm
Gene Expression Regulation
Gene Rearrangement, B-Lymphocyte
Genes, Switch
Genes, myc
Genetic Predisposition to Disease
Granuloma
Immunoglobulin Heavy Chains
Mice
Mice, Inbred BALB C
Peritonitis
Plasmacytoma
Polymerase Chain Reaction
Precancerous Conditions
Recombination, Genetic
Terpenes
Translocation, Genetic
jenkins-FCD Prod-404 0f9a74600e4e79798f8fa6f545ea115f3dd948b2