Molecular characterisation of JC virus strains detected in human brain tumours

AIMS: The aim of this study was to evaluate the presence and significance of JC virus (JCV) in human brain tumours. METHODS: Histology, immunohistochemistry (IHC) and molecular biology techniques were employed to examine specimens of tumour tissue, peripheral blood and cerebrospinal fluid taken from 22 patients with primary neuro-epithelial tumours. Furthermore, the coding viral protein (VP1) region and non-coding transcription control region (TCR) of JCV genome isolated from the tumours were submitted to sequence analysis in order to detect viral rearrangements or mutations. RESULTS: JCV genome was found in nine of the 22 tumour specimens (40.9%), including eight astrocyte-derived tumours (seven glioblastomas and one astrocytoma) and one oligodendroglioma, and in two of the 15 cerebrospinal fluid specimens (13.3%) with positive tumour tissue (one glioblastoma and one astrocytoma). Sequence analysis of JCV VP1, which was amplified in seven tissue samples and the two cerebrospinal fluid samples, revealed only genotype 1 (four 1a and three 1b), whereas TCR was amplified in six tissue samples and only one cerebrospinal fluid sample. TCR sequence analysis was possible in four cases and identified three Mad-4 and one type II sequences; the TCR genomic structures of JCV isolated from cerebrospinal fluid were the same as those sequenced from corresponding tumour tissue, thus indicating a possible cerebrospinal fluid dissemination of neoplastic cells carrying viral DNA. CONCLUSIONS: Our results suggest a possible role of JCV in the induction of brain tumours, especially in those originating from brain cells normally targeted by JCV infection.