Switching on chromosomal translocations.
Activation-induced deaminase initiates three different antibody diversification reactions: class switch recombination, somatic hypermutation (SHM), and gene conversion. We have shown that, in addition to antibody diversification, activation-induced deaminase can also initiate Burkitt's lymphoma-like c-myc/IgH translocations. However, distinct DNA damage- and oncogene-induced checkpoints operate in B cells to produce a normal intrachromosomal class switch recombination event or an aberrant interchromosomal fusion. These findings open the way to study the molecular pathways taking place at the early stages of malignant transformation.
Ramiro
Almudena R
AR
DNA Hypermutation Group, Spanish National Cancer Center, Madrid, Spain. arodriguezr@cnio.es
Nussenzweig
Michel C
MC
Nussenzweig
André
A
D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D014178:Translocation, Genetic