[Molecular genetic analysis of malignant lymphoma]

A semi-nested polymerase chain reaction for the variable region of the immunoglobulin heavy and light chain genes (VH, V kappa and V lambda) was used to investigate the cell of origin and the clonal history in intravascular malignant lymphomatosis (IML), primary central nervous system lymphoma (PCNSL) and diffuse large B-cell lymphoma (DLBCL). A monoclonal band of VH and V kappa genes was detected in all cases of IML. A monoclonal band of VH was also detected in PCNSL and DLBCL. The nucleotide sequences of the VH and V kappa genes were determined. Numerous point mutations were present in all of the VH and V kappa genes. Ongoing mutation was observed in 3 of 5 IML cases, in 1 of 5 PCNSL and in 4 of 12 DLBCL. Because the process of immunoglobulin gene hypermutation is thought to occur at the germinal center (GC) stage of B cell development, these results suggest that IML, PCNSL and DLBCL are derived from GC B cells or their descendants. Using this reliable and sensitive method, a monoclonal band was detected in peripheral blood samples from 5 IML cases. The diagnosis of IML was confirmed by biopsies or autopsies in 4 cases. The sequences obtained from biopsied tissues and blood samples were found to be identical in each case in 3 cases examined.