Detection of human neurotropic JC virus DNA sequence and expression of the viral oncogenic protein in pediatric medulloblastomas

Detection of human neurotropic JC virus DNA sequence and expression of the viral oncogenic protein in pediatric medulloblastomas

^*Center for NeuroVirology and NeuroOncology, MCP Hahnemann University, Philadelphia, PA 19102; ^†St. Christopher’s Hospital for Children, MCP Hahnemann University, Philadelphia, PA 19134; ^‡Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL 60153; and ^§Sbarro Institute for Cancer Research, Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107

Edited by James V. Neel, University of Michigan Medical School, Ann Arbor, MI, and approved July 7, 1999 (received for review April 20, 1999)

Abstract

Medulloblastoma represents greater than 25% of childhood intracranial neoplasms and is considered a highly malignant tumor. This tumor, which arises predominantly in the cerebellar vermis, preferentially affects children between the ages of 5 and 15. Although the etiology of medulloblastomas in humans remains unknown, results from several experiments have indicated that the human neurotropic JC virus (JCV) is able to induce cerebellar neoplasms in rodents that exhibit a phenotype similar to that of human medulloblastomas. JCV is a polyomavirus that is widespread in the human population, with infection occurring most frequently in early childhood. In this study, we have examined the possible association of JCV with human medulloblastomas. By using PCR techniques we demonstrate that 11 of 23 samples of tumor tissue contain DNA sequences corresponding to three different regions of the JCV genome. More importantly, we demonstrate the presence of DNA sequences encoding the N- and C-terminal regions of the JCV oncogenic protein, T antigen, in 11 of 23 samples and the production of T antigen in the nuclei of 4 samples of tumor tissue. These observations provide evidence for a possible association of JCV with human medulloblastomas.

Footnotes

↵ ¶ To whom reprint requests should be addressed at: Center for Neurovirology and Cancer Biology, Temple University, 1900 North 12th Street, Room 203-N, Philadelphia, PA 19122.
This paper was submitted directly (Track II) to the Proceedings Office.
ABBREVIATIONS:

PML,

progressive multifocal leukoencephalopathy;

CNS,

central nervous system;

JCV,

human neurotropic JC virus