Molecular pathology of lymphomas.

Chromosomal translocations appear to be the initiating step in the development of malignancy in both B cell and T cell lymphomas. These results in the juxtapositioning of proto-oncogenes and transcriptional factors to the IG or TCR genes and lead to the deregulation of their expression. A survival advantage is provided to the lymphoid cells and contributes to neoplasm by permitting a clone to persist until other oncogenes such as c-myc are activated. This suggests a multistep progression to tumorigenesis. The occurrence of these translocations is assisted by obligatory DNA breaks and rearrangements of IG and TCR that have to occur for B and T cells to mature and function. The molecular alterations specific to lymphomas provide a potential specific target for therapy, including molecular manipulations. Animal modelling of lymphoma will provide the greatest possibilities for investigating the pathogenesis of lymphoma and future treatment modalities.