High frequency of somatic mutations in VH Genes expressed in intraocular lymphoma.

Abstract

Abstract: : Purpose: To investigate the cell origin of the intraocular lymphoma. Methods: We have analysed VH gene sequences of 6 cases of ocular lymphoma, using the polymerase chain reaction (PCR) method to amplify the immunoglobulin heavy chain (IgH) gene of DNA extracted from vitreous cells. Results: Cytological studies from vitreous samples confirmed to be large B–cell lymphoma in 6 cases. The mean age was 69.4 years and the F/M ratio was 5/1. Four patients presented primary intraocular lymphoma and two patients presented central nervous system and intraocular lymphoma. All VH genes were found to have accumulated high levels of somatic mutations (12.4 to 17%). Of the 6 cases, 4 used the VH 4–34 gene segment. In 5 of 6 cases, intraclonal nucleotide heterogeneity was observed, indicating that the VH genes were still under the influence of the somatic hypermutation mechanism. Analysis of the distribution of silent and replacement mutations showed evidence for preservation of immunoglobulin structure in 4 cases. Conclusions: This is the first VH gene sequence analysis in primary ocular lymphoma. These results are similar to those observed in primary central nervous system lymphomas. They suggest that, although there is no evidence for germinal center formation in the ocular tissues, intraocular lymphoma is derived from a B cell with features associated with location in a germinal center environment.

Keywords: tumors • cytology • gene screening