Luis Del Valle, M.D., and Kamel Khalili, Ph.D., of Temple University in Philadelphia, and their coworkers found that some medulloblastomas contain only agnoprotein and not T antigen, another protein believed to play a role in the development of several types of brain tumors. Their findings appear in the Feb. 20 issue of the Journal of the National Cancer Institute.
Both agnoprotein and T antigen are protein products of the JC virus (JCV), a human polyomavirus that can cause progressive multifocal leukoencephalopathy (PML), a fatal disease frequently seen in AIDS patients. In the absence of PML, JCV may stimulate rapid and uncontrolled cell growth, leading to cancer, the authors note. The virus is transmitted early in life, infecting 65% of children by the age of 14. The virus is most likely transmitted through the parent, the authors note, and may enter a child's developing brain through infected B cells.
T antigen may cause brain tumors in part by blocking tumor suppressor proteins such as p53 and pRb. The role of agnoprotein in the development of brain tumors is unknown. Recent studies suggest, however, that the interaction of T antigen with agnoprotein may effect T antigen's ability to enhance replication of the viral genes.
In the current study, the authors found the presence of the gene that encodes agnoprotein in 69% of 16 medulloblastoma samples, and T antigen DNA in 65% of 20 medulloblastoma samples. The authors found agnoprotein and T antigen in 45% of 20 medulloblastoma samples; 2 out of the 20 samples contained only agnoprotein. The authors conclude that "the finding of agnoprotein expression in the absence of T antigen expression suggests a potential role for agnoprotein in pathways involved in the development of JCV-associated medulloblastomas."
In a related editorial, Howard A. Fine, M.D, of the Neuro-Oncology Branch of the National Cancer Institute and the National Institute of Neurologic Disorders and Stroke says this is a "provocative assertion," but cautions that, "the presence of these sequences in tumor cells may merely represent genetic remnants of a prior abortive infection in an earlier progenitor cell that ultimately happened to turn tumorigenic."
Contact: Preston Moretz, Temple University, (215) 204-7476; fax: (215) 204-4403, pmoretz@temple.edu
Editorial: NCI Press Office, (301) 496-6641
Del Valle L, Gordon J, Enam S, Delbue S, Croul S, Abraham S, Radhakrishnan S, Assimakapoulou M, Katsetos CD, Khalili K. Expression of human polyomavirus JCV late gene product agnoprotein in human medulloblastoma. J Natl Cancer Inst 2002;94:267–73.
Editorial: Fine HA. Polyomavirus and medulloblastoma: a smoking gun or guilt by association? J Natl Cancer Inst 2002;94:240–1.
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