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

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.

Activation of the IGF-IR system contributes to malignant growth of human and mouse medulloblastomas

“…In contrast, quiescent mouse Bs-1b, Bs-1c, BsB8 cells (Figure 2b,d,f) and human D283 Med cells (Figure 2j), tested with the antipY1316 antibody showed much weaker di use staining, similar to the background staining obtained when the primary antibody was omitted from the reaction (Figure 2i picture B). These results indicate that anti- (Krynska et al, 1999).…”

Investigation of the simian polyomavirus SV40 as a potential causative agent of human neurological disorders in AIDS patients

“…Polyomavirus Tag has several biochemical and biological properties: ATPase, helicase, clastogenic and mutagenic activities; it induces cellular and viral DNA replication and it binds tumour suppressor gene products such as p53 and pRb [9]. Although no direct roles for JCV in the onset or progression of human brain tumours were assessed, recent studies found JCV DNA associated with brain neoplasms in the absence of PML [12,48,49]. SV40 sequences have been detected in human brain tumours of different histological types and other human neoplasms by several investigators [9].…”

“…Human JCV is the causative agent of PML [11], and JCV DNA sequences and its large T antigen (Tag) oncoprotein have been detected in human medulloblastomas [12]. BKV is associated with diseases of immunocompromised patients, and has been detected in the brain and cerebrospinal¯uid (CSF) of an AIDS patient with meningo-encephalitis [13].…”

Association of SV40 with human tumors

“…Barbara Krynska (MCP Hannemann University, Philadelphia, USA) reported that JC virus was present in 11/23 medulloblastomas tested (Krynska et al, 1999) and 5/11 JC containing medulloblastomas also contained SV40 sequences. Production of the JC virus tumor antigen was detected in the nuclei of four of these tumors.…”