A number of issues will be addressed that relate to human lymphoid neoplasia and range from subjects that are highly clinical to those that are of a basic biologic nature. Among the clinical topics is an investigation into the cellular composition of Hodgkin's disease and lymphomatoid papulosis by analyzing rearrangements of immunoglobulin and T cell receptor genes in tissues from patients with these disorders. Gene rearrangements will also be used to detect small amounts of tumor cells in peripheral blood of patients with lymphoma and mycosis fungoides and in bone marrow of patients with lymphoma. Small amounts of tumor cells circulating in the blood or in the bone marrow, as well as the possible occurence of multiple neoplastic clones, will be correlated with clinical data, such as rates of relapse and survival over time. More basic projects include studies concerning two chromosomal translocations in lymphoid neoplasms - the t(14;18) translocation of follicular lymphomas and a t(7;9) translocation in T cell leukemias. In the former translocation, attention will focus on a recently discovered second cluster of chromosome 18 breakpoints distinct from the cluster region on chromosome 18 in which most t(14;18) breakpoints occur. DNA structure and transcription from loci around this second cluster region will be analyzed using DNA that we have recently cloned from lymphoma cells. Analysis of DNA structure and transcription surrounding the breakpoints in the t(7;9) translocation will also be performed using DNA probes for beta T cell receptor and c-abl genes, which map close to the breakpoints in this translocation. A last set of studies concerns somatic mutation in immunoglobulin genes of lymphoid neoplasms. Multiple copies of rearranged genes will be cloned from individual pre-B, plasma cell, and myeloid neoplasms to assess the degree and position of possible somatic mutations and to determine (a) whether somatic mutation occurs in each of these tumors and, (b) whether clustering of mutations is observed in certain regions of the genes of pre-B cells independently of possible selection due to interaction of antigen or anti-idiotype with surface immunoglobulin. Somatic mutations of cloned immunoglobulin genes will also be examined among clonal B cells from patients with plasma cell neoplasms to investigate how myelomas may possibly evolve from populations of neoplastic or pre-neoplastic B cells.
