Alterations of the Immunoglobulin Heavy Chain Locus in Progressive B-cell Lymphomas

Twenty-two patients with relapsed or progressive B-cell lymphomas (BCL) were analysed for alterations in the rearrangement status in the immunoglobulin heavy (IgH) chain gene in samples obtained on different occasions during the course of the disease. The analysis was performed using Southern blot hybridization of the IgH gene and polymerase chain reaction (PCR) amplification of the VH gene families combined with single-strand conformation polymorphism (SSCP) analysis. Using Southern blot analysis, we found that all 22 lymphomas displayed clonal IgH rearrangements, and changes during tumour progression occurred in 8 cases. These alterations were mainly observed in cases with follicular or transformed lymphomas. More than one malignant (sub)clone, indicated by more than two rearranged bands, was detected in one case at diagnosis and in three cases at relapse. Outgrowth of subclones with divergent rearrangement patterns in different compartments was also observed in 2 out of 8 cases. PCR-SSCP analysis indicated that all 15 cases studied displayed clonal rearrangements and in 6 cases altered rearrangement patterns were detected in later samples. Southern blotting and PCR-SCCP analysis gave equivalent results. No association was found between time to relapse or survival time and alterations in rearrangement pattern. The present study illustrates that the neoplastic cell clones in BCL often display alterations in their IgH locus, but the significance of this feature remains to be clarified.