DNA rearrangements in non-Hodgkin's lymphomas.

The configuration of DNA at genetic loci that undergo somatic recombination in lymphocytes provides genetic markers that are useful in the diagnosis and characterization of non-Hodgkin's lymphomas. The loci containing rearranged DNA fall into three groups: the immunoglobulin genes, the T cell receptor genes and sites of chromosomal rearrangements, such as chromosomal translocations. DNA fragments cloned from these loci can be used as hybridization probes to characterize the rearranged DNA sequences in biopsy tissues. Only probes for chromosomal rearrangements are capable of directly diagnosing neoplasia and histological subtypes; however, probes for rearrangements of immunoglobulin and T cell receptor genes are valuable for detecting clonal proliferations, determining B or T cell derivation of tumours and distinguishing individual clones of lymphocytes from each other. Applications of DNA rearrangements have already yielded a number of important findings concerning the biology of human lymphoma. These discoveries have included the existence of multiclonal B cell cancers, the widespread dissemination of occult tumour to lymph nodes in mycosis fungoides, the high incidence of circulating tumour cells in patients with low grade lymphomas and the molecular heterogeneity of chromosomal break-points in follicular lymphomas.