Molecular epidemiology of deletions and mutations of the latent membrane protein 1 oncogene of the Epstein-Barr virus in posttransplant lymphoproliferative disorders.

Latent membrane protein 1 (LMP1) is a protooncogene of the Epstein-Barr virus (EBV) that is expressed in most EBV-positive posttransplant lymphoproliferative disorders (PTLD). Small deletions in the carboxy-terminal domain of LMP1 have been recently described in Hodgkin's disease, nasopharyngeal carcinoma, and non-Hodgkin's lymphoma. We characterized the deletions and point mutations of LMP1 in 32 PTLD and 8 reactive lymphoid cases found to contain EBV by one or more methods, including LMP1 immunohistochemistry, EBV-encoded RNA in situ hybridization, LMP1 DNA amplification, or Southern blot analysis. Our goal was to study the relationship of LMP1 deletions and mutations with the PTLD morphology, clonality, EBV strain subtype, and survival of patients. We found a 30-bp deletion (Del-LMP1) in 13 of 32 (41%) PTLD cases and a similar incidence of Del-LMP1 and point mutations in 3 of 8 (38%) reactive EBV cases (rho = 0.87). The presence of the Del-LMP1 in the PTLD cases was not highly associated with a high-grade morphology or clonal immunoglobulin gene rearrangements compared with the wild-type LMP1. We found that 100% of B-strain isolates, compared with 30% of A-strain isolates, harbored the Del-LMP1. There was no significant difference in the survival of PTLD patients with or without Del-LMP1 (rho = 0.83). We conclude that the incidence of Del-LMP1 in PTLD may be reflective of the incidence of this EBV substrain in the regional population and that the Del-LMP1 sequence has no prognostic significance in PTLD.