The present investigation will utilize the techniques of molecular genetics to develop an improved classification of human lymphoma with the goal of improving our ability to predict survival and select optimal therapy. 1. The configuration of the genes for the beta and gamma chains of the T-cell receptor (T beta and T gamma) will be determined in a spectrum of established T-cell malignancies, B-cell neoplasms including non-B, non-T acute lymphocytic leukemia, and in certain reactive processes in T cells. This data will be used to define the relationship of clonal rearrangement of the T-cell receptor to clinical neoplasia. 2. The diagnosis of B-cell lymphoma and chronic lymphocytic leukemia will be refined by employing Southern blot analysis of tumor DNA. Initially, the configuration of genes for the heavy and light chains of immunoglobulin (Ig) will be analyzed in the entire spectrum of adult (B-cell) lymphoma, includig at least 25 tumors of each major subtype and those with indeterminate immunotype. The status of the T-cell receptor genes will also be established in these tumors. Those lymphomas and lymphoma-like conditions which present difficulties in diagnosis or interpretation on the basis of microscopic study and surface markers will also be examined. 3. The results of molecular genetics will be incorporated into a lymphoma classification: in addition to the configuration of the Ig and T-cell receptor genes the status of bc1-1, bc1-2 and myc will be assessed with appropriate probes. The resulting classification will encompass (1) clinical, (2) pathological, and (3) surface marker features in addition to (4) molecular genetic studies. 4. The usefulness of Southern blot analysis of Ig and T-cell receptor genes will be evaluated in the clinic.
