DETECTION OF CLONAL IMMUNOGLOBULIN HEAVY-CHAIN GENE REARRANGEMENTS INCASES OF SUSPECTED LYMPHOPROLIFERATIVE DISORDERS - COMPARISON OF POLYMERASE CHAIN-REACTION AND SOUTHERN BLOT ANALYSIS

Demonstration of clonality is supportive of a diagnosis of malignancy in cases of lymphoproliferative disorders, Determination of clonality at the molecular level is currently accomplished by Southern analysis; however, the polymerase chain reaction offers a potential alternative that is rapid, simple, and less expensive. To test its feasibility as a diagnostic test, we amplified the DNA from 121 suspected lymphoprol iferative disorders submitted for gene rearrangement studies. In compa rison to Southern analyses, a sensitivity of 70% and specificity of 96 % were obtained. To test the effect of primer variability in the Joini ng region of the heavy-chain gene, we substituted a more degenerate pr imer but found no changes in sensitivity or specificity. We conclude t hat the polymerase chain reaction has current application with minute or fixed specimens and may generally serve as a rapid, initial evaluat ion for B-cell clonality, followed by Southern analysis in negative ca ses. However, higher overall sensitivity must be achieved before this technique can replace Southern analysis as the method of choice in det ermining clonal gene rearrangements.