Detection of JC virus DNA sequence and expression of the viral oncoprotein, tumor antigen, in brain of immunocompetent patient with oligoastrocytoma.
We describe molecular and clinical findings in an immunocompetent patient with an oligoastrocytoma and the concomitant presence of the human papovavirus, JC virus (JCV), which is the etiologic agent of the subacute, debilitating demyelinating disease, progressive multifocal leukoencephalopathy. Histologic review revealed a glial neoplasm consisting primarily of a moderately cellular oligodendroglioma with distinct areas of a fibrillary astrocytoma. Immunohistochemical analysis revealed nuclear staining of tumor cells with antibodies against the viral oncoprotein [tumor antigen (T antigen)], the proliferation marker (Ki67), and the cellular proliferation regulator (p53). Using primers specific to the JCV control region, PCR yielded amplified DNA that was identical to the control region of the Mad-4 strain of the virus. PCR analysis demonstrated the presence of the genome for the viral oncoprotein, T antigen, and results from primer extension studies revealed synthesis of the viral early RNA for T antigen in the tumor tissues. The presence of viral T antigen in the tumor tissue was further demonstrated by immunoblot assay. To our knowledge, this is the first report of the presence of JCV DNA, RNA, and T antigen in tissue in which viral T antigen is localized to tumor cell nuclei and suggests the possible association of JCV with some glial neoplasms.
Rencic
A
A
Molecular Neurovirology, Jefferson Institute of Molecular Medicine, Philadelphia, PA 19107, USA.
Gordon
J
J
Otte
J
J
Curtis
M
M
Kovatich
A
A
Zoltick
P
P
Khalili
K
K
Andrews
D
D
D000951:Antigens, Neoplasm / Q000032:analysis; D000957:Antigens, Viral, Tumor / Q000032:analysis; D001254:Astrocytoma / Q000473:pathology / Q000601:surgery / Q000821:virology; D001483:Base Sequence; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery / Q000821:virology*; D017931:DNA Primers; D004279:DNA, Viral / Q000032:analysis; D005910:Glioma / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery / Q000821:virology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007577:JC Virus / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D019394:Ki-67 Antigen; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D009837:Oligodendroglioma / Q000473:pathology / Q000601:surgery / Q000821:virology; D016133:Polymerase Chain Reaction; D012045:Regulatory Sequences, Nucleic Acid; D018741:Replication Origin; D014057:Tomography, X-Ray Computed; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000951:Antigens, Neoplasm; D000957:Antigens, Viral, Tumor; D017931:DNA Primers; D004279:DNA, Viral; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53