Immunoglobulin gene rearrangement as a diagnostic criterion of B-cell lymphoma.

Abstract

The use of the Southern blot hybridization technique to diagnose [human] B-cell lymphoma by detecting clonal Ig gene rearrangements in lymph node and other biopsy tissues is described. DNA was isolated from a wide variety of neoplastic and non-neoplastic specimens and analyzed for the presence of rearranged Ig genes using radiolabeled DNA probes specific for the heavy- and LIg constant region genes. Among the specimens examined, clonal Ig gene rearrangements were found only in biopsy samples of B cell lymphoma and not in samples containing reactive lymphoid processes or non B cell cancers. In lymphomas, the presence of rearrangements for either the .kappa. or .lambda. l chain gene correlated with expression of one or the other of these chains when cellular Ig could be detected by frozen-section immunophenotyping techniques. The analysis of Ig gene rearrangements offers several advantages over conventional diagnostic methods for lymphomas, including improved sensitivity in detecting minor populations of neoplastic lymphocytes composing as little as 1% of the total cell population. Clonal Ig gene rearrangements are demonstrable in a subset of lymphomas that lack detectable surface or cytoplasmic Ig, thus offering positive evidence for both malignancy and the B cell origin of these tumors. Detection of Ig gene rearrangements is a valuable method for diagnosis and classification of various lymphoproliferative disorders that are difficult to evaluate histologically or that lack distinctive antigenic markers.