SV40 in human brain cancers and non-Hodgkin's lymphoma

Vilchez, Regis A.; Butel, Janet S.

doi:10.1038/sj.onc.1206547

Cited by 45 publications

(31 citation statements)

References 72 publications

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“…Molecular and pathological data suggest an involvement of SV40 in CNS tumours but its functional or aetiological significance remains unclear [Vilchez and Butel, 2003]. The epidemiology of these neurotropic viruses is also not apparent and cannot therefore offer support for their causative role in CNS tumours in humans.…”

Section: Immune Factorsmentioning

confidence: 98%

Central nervous system tumours in children: Epidemiology and risk factors

McKinney

2005

Bioelectromagnetics

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In children, a variety of distinct tumour types arise in the central nervous system (CNS) but they are frequently considered by epidemiologists as a single entity. CNS tumours are the second most common childhood malignancy and occur more frequently in developed countries than developing nations. Approximately 50% of paediatric CNS tumours are gliomas, with astrocytomas of the piloctyic type predominating. Distributions of subtypes by age show that primitive neuroectodermal tumours (PNET) and ependymomas mainly occur in children less than 10 years. There is an ongoing debate with regard to the apparent increases in incidence over recent decades, which, it has been suggested, are accounted for by improved diagnostic technologies implemented in the mid 1980s. CNS tumours differ between children and adults with respect to the proportion of all cancers (20% in children, less than 2% in adults), their cellular origins, classification scheme, the proportions of pathological subtypes, and anatomic site. The causes of childhood CNS tumours are largely unknown; and although an estimated 5% or more may be explained by genetic predisposition, investigations of environmental aetiology have not been fruitful. Whilst high dose ionising radiation is an established risk factor for this group of tumours, reported associations with dietary N-nitroso compounds have not been consistent. Exposure to ELF EMF, at any level, has not been associated with childhood CNS tumours, but the current evidence base is inadequate for complete evaluation. The rarity of childhood CNS tumours necessitates careful attention being paid to the design of future aetiological studies.

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Section: Immune Factorsmentioning

confidence: 98%

Central nervous system tumours in children: Epidemiology and risk factors

McKinney

2005

Bioelectromagnetics

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“…Variations in the T-ag-C gene region were frequently detected in human tumor-associated sequences, ruling out the possibility that positive findings were the result of laboratory contamination of specimens (4,7,26,27,40,(44)(45)(46). The T-ag-C sequence was shown to be stable during tissue culture passage of SV40 isolates (24).…”

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confidence: 97%

Phylogenetic Analysis of Polyomavirus Simian Virus 40 from Monkeys and Humans Reveals Genetic Variation

Forsman

Lednicky

Fox

et al. 2004

J Virol

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A phylogenetic analysis of 14 complete simian virus 40 (SV40) genomes was conducted in order to determine strain relatedness and the extent of genetic variation. This analysis included infectious isolates recovered between 1960 and 1999 from primary cultures of monkey kidney cells, from contaminated poliovaccines and an adenovirus seed stock, from human malignancies, and from transformed human cells. Maximum-parsimony and distance methods revealed distinct SV40 clades. However, no clear patterns of association between genotype and viral source were apparent. One clade (clade A) is derived from strain 776, the reference strain of SV40. Clade B contains isolates from poliovaccines (strains 777 and Baylor), from monkeys (strains N128, Rh911, and K661), and from human tumors (strains SVCPC and SVMEN). Thus, adaptation is not essential for SV40 survival in humans. The C terminus of the T-antigen (T-ag-C) gene contains the highest proportion of variable sites in the SV40 genome. An analysis based on just the T-ag-C region was highly congruent with the whole-genome analysis; hence, sequencing of just this one region is useful in strain identification. Analysis of an additional 16 strains for which only the T-ag-C gene was sequenced indicated that further SV40 genetic diversity is likely, resulting in a provisional clade (clade C) that currently contains strains associated with human tumors and human strain PML-1. Four other polymorphic regions in the genome were also identified. If these regions were analyzed in conjunction with the T-ag-C region, most of the phylogenetic signal could be captured without complete genome sequencing. This report represents the first whole-genome approach to establishing phylogenetic relatedness among different strains of SV40. It will be important in the future to develop a more complete catalog of SV40 variation in its natural monkey host, to determine if SV40 strains from different clades vary in biological or pathogenic properties, and to identify which SV40 strains are transmissible among humans.

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“…However, the discovery of a viral implication in CNS tumorigenesis may open different ways for preventing tumours with a constant fatal outcome such as glioblastomas. Accumulating data seem to indicate that SV40 is implicated in different tumours in humans and in particular in central nervous system (CNS) (Bergsagel et al, 1992;Klein et al, 2002;Carbone et al, 2003;Vilchez and Butel, 2003) However, there are strong controversies as to whether SV40 is directly linked to cancer development and a consensus is far from being reached in particular in lymphoma (Shivapurkar et al, 2002;Vilchez et al, 2002;Capello et al, 2003;MacKenzie et al, 2003).…”

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confidence: 99%

Detection of human cytomegalovirus genome and gene products in central nervous system tumours

et al. 2005

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Human cytomegalovirus (HCMV) genome and related proteins have been reported in a great proportion of malignant gliomas. However, these results are unexpected since HCMV is not known as an oncogenic virus. By immunohistochemistry (with an anti-IE1 monoclonal antibody) and in situ hybridisation (with biotinylated DNA probes) on tissue microarrays and frozen sections, we investigated a French series of central nervous system (CNS) tumours, including 97 glioblastomas. In 10 cases of glioblastoma, rare astrocyte-like cells, admixed with tumour cells, stained positively for HCMV and in one case a doubtful staining of rare cells was noticed. This may indicate a reactivation of the virus under local immunosuppression but none of the cases of CNS tumours (n ¼ 132) contained HCMV genomes and/or proteins in a significant proportion of tumour cells. Our results strongly suggest that HCMV is unlikely to be implicated in the development of human malignant gliomas, at least in French cases.

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SV40 in human brain cancers and non-Hodgkin's lymphoma

Cited by 45 publications

References 72 publications

Central nervous system tumours in children: Epidemiology and risk factors

Central nervous system tumours in children: Epidemiology and risk factors

Phylogenetic Analysis of Polyomavirus Simian Virus 40 from Monkeys and Humans Reveals Genetic Variation

Detection of human cytomegalovirus genome and gene products in central nervous system tumours

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