PMID- 10377173
OWN - NLM
STAT- MEDLINE
DCOM- 19990707
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 103
IP  - 12
DP  - 1999 Jun
TI  - Genetic pathway to recurrent chromosome translocations in murine lymphoma 
      involves V(D)J recombinase.
PG  - 1669-75
AB  - Chromosome translocations involving antigen receptor loci are a genetic hallmark 
      of non-Hodgkin's lymphomas in humans. Most commonly, these translocations result 
      in juxtaposition of the immunoglobulin heavy-chain (IgH) locus with one of 
      several cellular proto-oncogenes, leading to deregulated oncogene expression. The 
      V(D)J recombinase, which mediates physiologic rearrangements of antigen receptor 
      genes, may play a mechanistic role in some lymphoma translocations, although 
      evidence is indirect. A high incidence of B-lineage lymphomas has been observed 
      in mice with severe combined immunodeficiency (SCID) and p53-null mutations. We 
      show that these tumors are characteristic of the pro-B-cell stage of development 
      and that they harbor recurrent translocations involving chromosomes 12 and 15. 
      Fluorescence in situ hybridization (FISH) shows retention of IgH sequences on the 
      derivative chromosome 12, implying that breakpoints involve the IgH locus. 
      Pro-B-cell lymphomas were suppressed in SCID p53(-/-) mice by a Rag-2-null 
      mutation, demonstrating that DNA breaks generated during V(D)J recombination are 
      required for oncogenic transformation, and suggesting that t(12;15) arise during 
      attempted IgH rearrangement in pro-B cells. These studies indicate that the 
      oncogenic potential inherent in antigen receptor diversification is controlled in 
      vivo by efficient rejoining of DNA ends generated during V(D)J recombination and 
      an intact cellular response to DNA damage.
FAU - Vanasse, G J
AU  - Vanasse GJ
AD  - Department of Medicine, University of Washington, Seattle 98195, USA.
FAU - Halbrook, J
AU  - Halbrook J
FAU - Thomas, S
AU  - Thomas S
FAU - Burgess, A
AU  - Burgess A
FAU - Hoekstra, M F
AU  - Hoekstra MF
FAU - Disteche, C M
AU  - Disteche CM
FAU - Willerford, D M
AU  - Willerford DM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Immunoglobulin Heavy Chains)
RN  - 0 (Receptors, Antigen, B-Cell)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.7.- (DNA Nucleotidyltransferases)
RN  - EC 2.7.7.- (VDJ Recombinases)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/immunology
MH  - DNA Nucleotidyltransferases/*genetics
MH  - Gene Rearrangement, B-Lymphocyte, Heavy Chain
MH  - Immunoglobulin Heavy Chains/genetics
MH  - Immunophenotyping
MH  - Lymphoma, B-Cell/*enzymology/*genetics/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred ICR
MH  - Mice, Knockout
MH  - Mice, SCID
MH  - Receptors, Antigen, B-Cell/genetics
MH  - Stem Cells/immunology
MH  - *Translocation, Genetic/immunology
MH  - Tumor Suppressor Protein p53/deficiency/genetics
MH  - VDJ Recombinases
PMC - PMC408389
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
PMCR- 1999/06/15
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
PHST- 1999/06/15 00:00 [pmc-release]
AID - 06658 [pii]
AID - 10.1172/JCI6658 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Jun;103(12):1669-75. doi: 10.1172/JCI6658.