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Novel Molecular, Epidemiological, and Therapeutic Issues in Mesothelioma: The Role of SV40

The rise in mesothelioma cases that has occurred since 1950 has been associated with the widespread commercial use of asbestos. However, less than 10% of asbestos workers exposed to high levels of asbestos actually develop the disease, suggesting that additional factors may increase an individual’s susceptibility to the carcinogenic effects of asbestos.
In addition, about 20% of mesotheliomas are not associated with asbestos exposure, suggesting that alternative factors may also cause mesothelioma.

* The SV40

SV40 is a DNA tumour virus which was introduced into a significant portion of the human population between 1955 and 1963 through polio vaccines and adenovaccines
contaminated with the virus.


SV40 and human tumours

The discovery that SV40 produced tumours in hamsters led to the PCR analysis of human mesotheliomas for the presence of SV40. Our group was the first to investigate whether there was any correlation between Polyomavirus and mesothelioma, and this was accom- plished in two separate series of patients.
DNA was extracted from 48 frozen human mesothelioma specimens and 2 benign fibrous tumours of pleura (FTP) from patients undergoing resection of their tumours at the National Cancer Institute, Bethesda, Maryland. In 28 instances, the corresponding DNA was extracted from lung tissue not infiltrated with mesothelioma.

To resolve ambiguities regarding the possible confusion with other papovavi- ruses, mesothelioma samples were analysed by direct DNA sequencing with the primers Pyv.for and Pyv.rev. These primers were previously described by Bergsagel et al. to identify SV40-like sequences in human ependymomas.
These primers amplify a 172 bp region of Tag containing the Rb-family binding domain common to several papovaviruses including SV40. The SV40 sequence, however, can be distinguished from the other papovaviruses because it lacks a 9 bp insert between positions 4516 and 4517. The sequences obtained from our three mesothelioma specimens lacked this 9 bp insert and were 95–97% homologous to SV40.

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