Mechanisms of chromosomal translocations in B cell lymphomas.
Reciprocal chromosomal translocations involving the immunoglobulin (Ig) loci are a hallmark of most mature B cell lymphomas and usually result in dysregulated expression of oncogenes brought under the control of the Ig enhancers. Although the precise mechanisms involved in the development of these translocations remains essentially unknown, a clear relationship has been established with the mechanisms that lead to Ig gene remodeling, including V(D)J recombination, isotype switching and somatic hypermutation. The common denominator of these three processes in the formation of Ig-associated translocations is probably represented by the fact that each of these processes intrinsically generates double-strand DNA breaks. Since isotype switching and somatic hypermutation occur in germinal center (GC) B cells, the origin of a large number of B cell lymphomas from GC B cells is likely closely related to aberrant hypermutation and isotype switching activity in these B cells.
Küppers
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R
Institute of Cancer Genetics, Columbia University, New York, NY 10032, USA. rkuppers@mac.genetik.uni-koeln.de
Dalla-Favera
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R
D000483:Alleles; D000818:Animals; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D011995:Recombination, Genetic; D014178:Translocation, Genetic; D045567:VDJ Recombinases
D007136:Immunoglobulins; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases