Book chapter
Genomic instability in B-cells and diversity of recombinations that activate c-myc
Mechanisms in B-Cell Neoplasia 1994, pp.373-380
Current topics in microbiology and immunology, 194, Springer
1995
DOI: 10.1007/978-3-642-79275-5_43
PMID: 7895512
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.
Details
- Title: Subtitle
- Genomic instability in B-cells and diversity of recombinations that activate c-myc
- Creators
- S Janz - Laboratory of Genetics, NCI, NIHG M JonesJ R MüllerM Potter
- Resource Type
- Book chapter
- Publication Details
- Mechanisms in B-Cell Neoplasia 1994, pp.373-380
- Publisher
- Springer; Hedelberg
- Series
- Current topics in microbiology and immunology; 194
- DOI
- 10.1007/978-3-642-79275-5_43
- PMID
- 7895512
- ISSN
- 0070-217X
- Language
- English
- Date published
- 1995
- Academic Unit
- Pathology
- Record Identifier
- 9984083201202771
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