Journal article
Differences in the molecular structure of c-myc-activating recombinations in murine plasmacytomas and precursor cells
Proceedings of the National Academy of Sciences - PNAS, Vol.91(25), pp.12066-12070
12/06/1994
DOI: 10.1073/pnas.91.25.12066
PMCID: PMC45377
PMID: 7991585
Abstract
The translocation of c-myc on chromosome (chr.) 15 to an immunoglobulin heavy-chain switch region on chr. 12 is the critical oncogenic step in pristane-induced plasmacytoma (PCT) development in BALB/cAnPt mice. Applying a recently developed PCR method, we have been able to detect the most commonly occurring illegitimate recombinations between alpha-chain switch region (S alpha) and c-myc in preneoplastic B cells residing in mesenteric oil granuloma (OG) tissues 7-30 days postpristane. In this study, we compare the nucleotide sequences at the S alpha/c-myc breaksites on both the c-myc-activating chr. 12+ and the reciprocal chr. 15- from eight transplanted PCTs, seven primary PCTs, and five OGs that contained six B-cell clones. These junction sequences revealed a remarkable diversity of S alpha/c-myc recombinations. In nine cases--four PCTs and five B-cell clones--nearly precise reciprocal exchanges with a loss of only 3-35 bp in c-myc were found. Large deletions in c-myc that removed 369-878 bp were observed in seven PCTs but not in early B cells. Duplications of c-myc ranging from 103 to 229 bp were also restricted to PCTs and noticed in four cases. Clonally related but different reciprocal recombinations, 38 bp apart on chr. 12+ and 15 bp apart on chr. 15-, were isolated from two different specimens of the same OG tissue from a BALB/c mouse 30 days postpristane. A second OG from another 30-day mouse yielded four recombinational fragments--two clonally related chr. 12(+)-specific fragments and two chr. 15(-)-specific fragments--one of which carried a 143-bp insertion of a microsatellite at the breaksite. We suggest that the initial recombinational break-point regions between S alpha and c-myc in plasmacytoma precursor cells at the time of immunoglobulin heavy-chain switching are intrinsically labile and characterized by a persisting instability of c-myc, which can result in large secondary deletions of c-myc.
Details
- Title: Subtitle
- Differences in the molecular structure of c-myc-activating recombinations in murine plasmacytomas and precursor cells
- Creators
- Jürgen R Müller - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892Michael Potter - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892Siegfried Janz - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.91(25), pp.12066-12070
- DOI
- 10.1073/pnas.91.25.12066
- PMID
- 7991585
- PMCID
- PMC45377
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 12/06/1994
- Academic Unit
- Pathology
- Record Identifier
- 9984083835102771
Metrics
25 Record Views