Use of the Polymerase Chain Reaction Technique to Detect the t(14;18) Translocation in Lymphoid Tissue

The t(14;18) (q32;21) chromosomal translocation is characteristic of follicle center cell lymphomas, involving 95% of cases (1 ,2 ). In addition, it has been found in a variety of other malignant lymphomas, including 20% of all diffuse B-cell lymphomas (3 ), diffuse small cleaved-cell lymphomas (4 ), and Hodgkin’s disease (5 –7 ). These observations have led to the theory that the t(14;18) (q32;21) translocation is a critical oncogenic event in the multiple-hit model of lymphomagenesis. The t(14;18) (q32;21) translocation juxtaposes the bcl-2 gene on chromosome 18 with the immunoglobulin heavy-chain joining region (J_H ) gene on chromosome 14 (8 ,9 ), resulting in deregulation and overexpression of the bcl-2 gene (10 ). Programmed cell death (apoptosis) is inhibited by bcl-2 protein, thus conferring a survival advantage to the lymphoma cells (11 ) The breakpoints on chromosome 14 and 18 are not random, but occur in specific, identified regions. The breakpoint on chromosome 18 is, in the majority of cases, clustered at two main regions in the bcl-2 gene: 50–60% in the 150-bp major breakpoint region (MBR) (12 ) and 25% in the minor cluster region (MCR) (13 ). The breakpoint on chromosome 14 always occurs within J_H , a small portion of the heavy-chain gene.