Mutation Analysis of IgVH Genes in Splenic Marginal Zone Lymphomas: Correlation with Clinical Characteristics and Outcome

Background: To determine the immunoglobulin variable heavy chain (IgVH) gene usage and somatic mutation patterns in a series of SMZL patients and to correlate these findings with the clinical features and outcome. Patients and Methods: IgVH genes were amplified and sequenced from 22 SMZL cases. Clinical and laboratory data of these patients were recorded. Results: A biased usage of IgVH gene was found with overrepresentation of VH3 in 16/22 cases. A total of 13/22 (59%) of cases were found to have mutated IgVH genes, whereas 9/22 (41%) were unmutated. Positive antigen selection process was identified in two cases. Treatment was different between the cases with mutation and those without. No differences in clinical and laboratory characteristics, or survival were found between the mutated and unmutated cases. Conclusion: SMZL are characterized by marked molecular heterogeneity. A biased usage of certain sequences suggests antigen selection. Prognostic significance of mutational status was not confirmed in this study. However further studies are needed in order to confirm these results.