Identification in human brain tumors of DNA sequences specific for SV40 large T antigen

Simian virus 40 (SV40) sequences have recently been identified in a variety of human neoplasms, including mesothelioma, osteosarcoma, and brain tumors , but significant discrepancies exist regarding the frequency at which this occurs. The SV40 genome is 70% homologous to JC and BK, two related polyom aviruses that are highly prevalent in humans and which may cause in immune- compromised patients progressive multifocal leukoencephalopathy (PML) and c ystitis, respectively. We have established a specific and sensitive method to identify SV40 sequence in DNA extracted from histological sections, usin g PCR followed by Southern hybridization to probes specific to the large T region. We found SV40 large T antigen sequences in all brain tumor types in vestigated. High frequencies were found in low-grade astrocytomas, anaplast ic astrocytomas and secondary glioblastomas derived thereof (13/22, 59%) wh ile somewhat lower frequencies were found in gemistocytic astrocytomas (9/2 8, 32%) and oligodendrogliomas (3/12, 25%). Primary glioblastomas, giant ce ll glioblastomas, and gliosarcomas, which clinically develop de novo, conta ined SV40 sequences in 11-25% of cases. Presence of viral DNA was also obse rved in pediatric brain tumors, including ependymomas (9/16, 56%), choroid plexus papillomas (6/16, 38%), and medulloblastomas (5/17, 29%). In 8 tumor biopsies with SV40 sequences, the adjacent normal brain tissue was also an alyzed but was devoid of viral DNA in all but one case. BK and JC virus seq uences were rarely detected, the overall frequencies being 3% and 2%, respe ctively. It remains to be shown whether the presence of SV40 contributes si gnificantly to malignant transformation or whether certain human neoplasms provide a microenvironment that favors viral replication in humans with lat ent SV40 infection.