Detection of immunoglobulin κ light chain rearrangements by polymerase chain reaction -: An improved method for detecting clonal B-cell lymphoproliferative disorders

The clonal determination of B-cell lymphoproliferative disorders by immunoglobulin heavy chain (IgH) rearrangement by polymerase chain. reaction (PCR) is widely used. However, few attempts have been made to detect Immunoglobulin. kappa light chain (Ig kappa) gene rearrangement using PCR, We studied 145 cases of B-cell neoplasms, along with 58 atypical and 18 reactive lymphoproliferative disorders, using newly designed degenerate oligoprimers recognizing the framework 3 (FR3 kappa) and the joint (J kappa) regions of the Ig kappa gene. PCR products were analyzed on nondenaturing polyacrylamide gel (ndPAGE), Clonal B-cell determination was further investigated using IgH rearrangement and t(11:14) or t(14:18). By combining these methods, we detected either clonality or translocation in 117 of 137 cases (85%) in mature B-cell neoplasms. The additional analysis of Ig kappa rearrangement improved sensitivity from 66% to 85%. To investigate whether the Ig gene configuration could be characterized using Ig kappa PCR in B-cell neoplasms showing severe breakdown of genomic DNA, 18 selected cases were analyzed. Successful amplification was detected in 72% of the cases using either FR3/2-JH and/or FR3J kappa oligoprimers, Finally, clonality was detected in 21 of 58 atypical B-cell proliferations, and among them, the atypical marginal cell. (54%) and atypical large cell (50%) proliferations showed the highest frequency of clonal immunoglobulin gene products. We concluded that PCR/ndPAGE analysis of Ig kappa is a sensitive, rapid, and efficient method for assessing clonality in. conjunction with IgH and specific translocation analysis. This approach is particularly useful in the characterization of B-cell lymphoproliferative disorders in archival material with poor preservation of the genomic DNA.