Genomic instability in B-cells and diversity of recombinations that activate c-myc. Curr Top Microbiol Immunol 1995;194:373-80
Date
01/01/1995Pubmed ID
7895512DOI
10.1007/978-3-642-79275-5_43Scopus ID
2-s2.0-0027988617 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
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 MAuthor
Siegfried Janz MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsB-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