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-Bar r virus (EBV) that is expressed in most EBV-positive posttransplant ly mphoproliferative disorders (PTLD). Small deletions in the carboxy-ter minal domain of LMP1 have been recently described in Hodgkin's disease , nasopharyngeal carcinoma, and non-Hodgkin's lymphoma. We characteriz ed 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, LMP 1 DNA amplification, or Southern blot analysis. Our goal was to study the relationship of LMP1 deletions and mutations with the PTLD morphol ogy, 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 simila r incidence of Del-LMP1 and point mutations in 3 of 8 (38%) reactive E BV cases (p = 0.87). The presence of the Del-LMP1 in the PTLD cases wa s not highly associated with a high-grade morphology or clonal immunog lobulin gene rearrangements compared with the wild-type LMP1. We found that 100% of B-strain isolates, compared with 30% of A-strain isolate s, harbored the Del-LMP1. There was no significant difference in the s urvival of PTLD patients with or without Del-LMP1 (p = 0.83). We concl ude that the incidence of Del-LMP1 in PTLD may be reflective of the in cidence of this EBV substrain in the regional population and that the Del-LMP1 sequence has no prognostic significance in PTLD.