Thymic carcinoma with a defective Epstein-Barr virus encoding the BZLF1 trans-activator.
The diagnosis of Epstein-Barr virus (EBV)-associated carcinomas is often heralded by high antibody titers to the viral replicative antigens, suggesting EBV reactivation may be a factor in tumor evolution. EBV DNA and nuclear antigen was detected in a newly diagnosed thymic carcinoma. Polymerase chain reaction analysis revealed the presence of a rearranged 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. Molecular analysis of the EBV termini demonstrated low levels of the lytic (linear) genomic configuration among a predominantly latent (episomal) population at diagnosis. The episomal populations were of uniform molecular 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 perhaps cellular gene regulation, suggests a potential mechanism for EBV reactivation and concurrent malignant progression.
Dept. of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, TN 38101-0318.
D F
DF
Patton
R C
RC
Ribeiro
J J
JJ
Jenkins
J W
JW
Sixbey
D000293:Adolescent; D001483:Base Sequence; D004279:DNA, Viral / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D003673:Defective Viruses / Q000235:genetics; D006566:Herpesviridae Infections / Q000382:microbiology*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013953:Thymus Neoplasms / Q000382:microbiology*; D015534:Trans-Activators / Q000235:genetics*; D014412:Tumor Virus Infections / Q000382:microbiology*; D014764:Viral Proteins / Q000235:genetics*; D014775:Virus Activation
C063676:BZLF1 protein, Herpesvirus 4, Human; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D015534:Trans-Activators; D014764:Viral Proteins