Rearrangements of immunoglobulin gene and oncogenes in ocular adnexal pseudolymphoma

Abstract

The organization of immunoglobulin heavy chain (IgH), light chain (kappa and lambda) and T cell receptor (TCR) beta chain gene loci in 10 patients with ocular adnexal pseudolymphoma was investigated. Eight of them showed IgH gene rearrangement in at least one of the 3 restriction enzymes-digested DNAs extracted from ocular adnexal neoplasms. In contrast, none of them exhibited clonal TCR beta chain gene rearrangement. The configuration of bcl-1, bcl-2 and c-myc oncogenes was also studied by Southern blot technique. Two patients had a rearranged joining region, IgH-containing fragment that comigrated with the rearranged bcl-1 fragment. C-myc gene rearrangement was found in only one patient who also had bcl-1 gene rearrangement. In ocular adnexal pseudolymphoma, none demonstrated bcl-2 gene rearrangement; however, in bone marrow cells, one patient with systemic lymphadenopathy exhibited both IgH and bcl-2 gene rearrangements. Three genotypic subsets of these ocular adnexal pseudolymphoma can be identified by the configuration of IgH gene and related oncogenes: with germline configuration of IgH gene and bcl-1, bcl-2 and c-myc oncogenes; with rearrangement of IgH gene but germline configuration of these oncogenes; and with recombination between rearranged IgH and bcl-1 genes. These results suggest in ocular adnexal pseudolymphoma a spectrum of clonal change evolving from polyclonal to monoclonal B-population, and further to monoclonal B-population with rearranged bcl-1, c-myc and/or bcl-2 oncogenes.