Novel insights into the mechanism of t(14;18)(q32;q21) translocation in follicular lymphoma.

The t(14:18)(q32:q21) chromosomal translocation and the ensuing overexpression of the BCL-2 proto-oncogene are strongly associated with the pathogenesis of follicular lymphoma. At the molecular level, the translocation process arises from the illegitimate rearrangement between the BCL-2 proto-oncogene and the immunoglobulin heavy chain (IgH) locus. Due to the presence of the D(H) and J(H) gene segments from the IgH locus as well as de novo nucleotide additions at the breakpoints, the translocation process has been assumed to result from a mistake occurring during V(D)J recombination in early B-cells in the bone marrow. However, recent detailed molecular analyses of both the direct and reciprocal breakpoints have revealed that the t(14;18) translocation is a more complex process than previously thought, and have challenged this traditional view. Here we review these observations, and discuss the intriguing possibility that t(14;18) translocation could preferentially occur in the germinal centers during receptor revision, and involves both V(D)J recombination and somatic hypermutation mechanisms.