Detection of immunoglobulin kappa light chain rearrangements by polymerasechain reaction - An improved method for detecting clonal B-cell lymphoproliferative disorders

The clonal determination of B-cell lymphoproliferative disorders by immunog lobulin heavy chain (IgH) rearrangement by polymerase chain. reaction (PCR) is widely used. However, few attempts have been made to detect Immunoglobu lin. kappa light chain (Ig kappa) gene rearrangement using PCR, We studied 145 cases of B-cell neoplasms, along with 58 atypical and 18 reactive lymph oproliferative disorders, using newly designed degenerate oligoprimers reco gnizing the framework 3 (FR3 kappa) and the joint (J kappa) regions of the Ig kappa gene. PCR products were analyzed on nondenaturing polyacrylamide g el (ndPAGE), Clonal B-cell determination was further investigated using IgH rearrangement and t(11:14) or t(14:18). By combining these methods, we det ected either clonality or translocation in 117 of 137 cases (85%) in mature B-cell neoplasms. The additional analysis of Ig kappa rearrangement improv ed sensitivity from 66% to 85%. To investigate whether the Ig gene configur ation could be characterized using Ig kappa PCR in B-cell neoplasms showing severe breakdown of genomic DNA, 18 selected cases were analyzed. Successf ul 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 at ypical B-cell proliferations, and among them, the atypical marginal cell. ( 54%) and atypical large cell (50%) proliferations showed the highest freque ncy of clonal immunoglobulin gene products. We concluded that PCR/ndPAGE an alysis of Ig kappa is a sensitive, rapid, and efficient method for assessin g clonality in. conjunction with IgH and specific translocation analysis. T his approach is particularly useful in the characterization of B-cell lymph oproliferative disorders in archival material with poor preservation of the genomic DNA.