THYMIC CARCINOMA WITH A DEFECTIVE EPSTEIN-BARR-VIRUS ENCODING THE BZLF1 TRANSACTIVATOR

The diagnosis of Epstein-Barr virus (EBV)-associated carcinomas is oft en heralded by high antibody titers to the viral replicative antigens, suggesting EBV reactivation may be a factor in tumor evolution. EBV D NA and nuclear antigen was detected in a newly diagnosed thymic carcin oma. Polymerase chain reaction analysis revealed the presence of a rea rranged EBV DNA fragment, BamHI WZhet. This rearrangement is found in a defective EBV that up-regulates the BZLF1 (BamHI Z leftward reading frame) gene product in vitro and induces the EBV lytic cycle. Molecula r analysis of the EBV termini demonstrated low levels of the lytic (li near) genomic configuration among a predominantly latent (episomal) po pulation at diagnosis. The episomal populations were of uniform molecu lar weight at diagnosis and relapse, indicating clonal tumor expansion from a single EBV-infected progenitor. The presence within malignant epithelium of defective virus that can disrupt EBV latency, and perhap s cellular gene regulation, suggests a potential mechanism for EBV rea ctivation and concurrent malignant progression.