Molecular genetics of B-cell lymphomas: a review

Recent developments in the past decade such as the advent of recombinant DNA technology, discovery of immunoglobulin gene rearrangements and recognition of the association of specific cytogenetic abnormalities with certain lymphoma subtypes have led to a better understanding of lymphoproliferative disorders. As the vast majority (80%) of non-Hodgkin's lymphomas are of the B-cell subtype, this is the focus of the article. By definition, tumours are clonal proliferations of a single, abnormal cell. Hence, B-lymphoid malignancy represents a monoclonal proliferation of B-lymphocytes. Immunophenotyping may be used to establish clonality for B-cell proliferations but may fail in some cases where surface antigens are not expressed or if the malignant clone is obscured by reactive lymphoid cells. Molecular methods are far more sensitive and do not require gene expression for detection, hence they are increasingly used for clonality assessment. Either Southern blot analysis or polymerase chain reaction can be used for this purpose. These techniques can also be used to detect specific cytogenetic abnormalities associated with certain lymphomas such as the bcl-2 gene rearrangement and follicular lymphoma. This is useful in the subtyping of lymphomas in cases where morphologic diagnosis is uncertain. Thus, with growing awareness and availability of molecular DNA analysis, these techniques are increasingly employed for the diagnosis of lymphomas as well as for the detection of minimal residual disease.