title: Detection of the JC virus genome in lung cancers: possible role of the T-antigen in lung oncogenesis.
abstract: The JC virus (JCV) infects a large proportion of the population worldwide and 80% to 90% of adults are seropositive and it may be activated in immunodeficient patients, resulting in progressive multifocal leukoencephalopathy. Recent reports described the possibility of its oncogenetic role in several malignancies. To clarify whether JCV might have a potential role in the genesis of lung cancers, we investigated the presence of its genome in 62 tumors, along with 23 samples of normal lung tissue, targeting the T-antigen, VP, and Agnoprotein by nested polymerase chain reaction/Southern blotting followed by direct DNA sequencing. Immunohistochemistry was performed to assess links between p53 and beta-catenin in lung cancers and the presence of T-antigen. The T-antigen was detected in 25 of 62 lung cancers but only 4 of 23 normal lung samples (P=0.048). In total, the JCV genome was present in 33 of the lung cancers and 10 of the normal samples. Furthermore, T-antigen was found in cancer cells in metastatic lymph nodes in 3 of 4 cases (P=0.042) and was more frequently detected in adenocarcinomas than in squamous cell carcinomas (P=0.038). Immunohistochemistry showed significant correlations between T-antigen and p53 (P=0.022) and also nuclear detection of beta-catenin (P=0.021). It is concluded that the JCV genome might be present in cancer cells in approximately half of all Japanese lung cancer cases, and that the T-antigen may play a role in oncogenesis of lung cancers through inactivation of p53 and dysregulation of the Wnt signaling pathway.
authors: First Pathology Department, Faculty of Medicine, Toyama University, 2630 Sugitani, Toyama, Japan.
authors: Hekmat Osman
authors: HO
authors: Abdel-Aziz
authors: Yoshihiro
authors: Y
authors: Murai
authors: Mei
authors: M
authors: Hong
authors: Tomohiko
authors: T
authors: Kutsuna
authors: Hiroyuki
authors: H
authors: Takahashi
authors: Kazuhiro
authors: K
authors: Nomoto
authors: Shuichi
authors: S
authors: Murata
authors: Koichi
authors: K
authors: Tsuneyama
authors: Yasuo
authors: Y
authors: Takano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000957:Antigens, Viral, Tumor / Q000032:analysis* / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D016679:Genome, Viral; D006801:Humans; D007150:Immunohistochemistry; D007577:JC Virus / Q000235:genetics / Q000302:isolation & purification*; D008175:Lung Neoplasms / Q000821:virology*; D008297:Male; D017422:Sequence Analysis, DNA; D014412:Tumor Virus Infections / Q000821:virology*
chemical_list: D000957:Antigens, Viral, Tumor; D004279:DNA, Viral