Simian virus (SV) 40 like sequences in cell lines and tumour biopsies from Australian malignant mesotheliomas

Our plain-English summary of Simian virus (SV) 40 like sequences in cell lines and tumour biopsies from Australian malignant mesotheliomas, by B.R. McLaren, T. Haenel, S. Stevenson, et al (Australian and New Zealand Journal of Medicine, 2000).

The study

• Authors: B.R. McLaren, T. Haenel, S. Stevenson, S. Mukherjee, B.W. Robinson, R.A. Lake
• Journal: Australian and New Zealand Journal of Medicine
• Published: 2000;30(4):450-6
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Simian virus (SV) 40 sequences have been found in some, but not all studies of mesotheliomas. This virus is known to cause tumours in rodents but its role in human oncogenesis remains controversial.

Aims: The aim of this study therefore was to determine whether SV40 is associated with the development of mesotheliomas in Australia. The absence of the virus or its gene products in tissue derived from mesotheliomas would detract from this possibility.

Methods: We used polymerase chain reaction from three pairs of primers to amplify different regions of the large T antigen from DNA from cell lines and cDNA from both cell lines and an independent set of tumour biopsies from patients with mesothelioma.

Results: We examined five human mesothelioma cell lines that were established in our laboratories. In addition, we examined several tumour biopsies from seven different patients. SV40 like sequences were present in all the cell lines and in at least one sample from each of the patients examined.

Conclusions: The large T antigen of SV40 or an SV40 like virus is expressed in Australian mesotheliomas and therefore could be aetiologically-associated with tumourigenesis. Alternatively, these sequences could be expressed subsequent to the development of the disease.

In plain English

This laboratory study from the University of Western Australia in Perth looked for genetic sequences resembling simian virus 40 (SV40), a monkey virus, in Australian malignant mesotheliomas. The authors tested five mesothelioma cell lines grown from patients' pleural fluid. They also tested separate tumour biopsies from seven men, all recorded as asbestos-exposed, with three biopsies per patient taken on different days. They used three sets of PCR primers aimed at different parts of the virus's large T antigen gene. One primer set found nothing in any cell line or biopsy. With the second set, all five cell lines were positive and every patient had at least one positive biopsy. Three patients were positive in all three biopsies. With the third set, all cell lines were positive, but biopsy results varied and one patient had no positive sample. The authors concluded that SV40-like sequences are present in Australian mesotheliomas. They wrote that it remains to be shown whether the virus contributes to the cancer, or whether the tumour provides an environment that favours the virus multiplying in people who already carry a latent SV40 infection. They noted that the products might be artefacts and had not yet been confirmed by sequencing.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study using polymerase chain reaction (PCR) to look for SV40-like large T antigen sequences in mesothelioma cell lines and tumour biopsies
• Who was studied: Five human malignant mesothelioma cell lines (Ju77, L068, No36, One58, Sty51) established from patients' pleural fluid. A separate set of tumour biopsies came from seven patients with histologically confirmed malignant mesothelioma in a gene therapy trial in Perth, Western Australia. According to Table 1, all seven were male and aged 53 to 70 at diagnosis. Three biopsies taken on different days were analysed per patient. Patient 4 was excluded because the samples were of poor quality. Collection dates are not given.
• Exposure: The study tested for SV40 or SV40-like virus large T antigen sequences, using three primer pairs that amplify different regions of the gene. Table 1 records asbestos exposure as 'Yes' for all seven biopsy patients. No fiber types, products, jobs or doses are given.
• Main results:
  • With the Svfor2/Svrev primers (574 base-pair fragment), all five cell lines and all tumour biopsies were negative. The SV40-transformed control cell line Met5A was positive.
  • All five cell lines were positive with the Svfor3/Svrev primers (105 base-pair fragment). The text reports they were also positive with the Sv8/Sv9 primers (289 base-pair fragment).
  • In the biopsies, SV40-like sequences were found in some samples from each patient but not in other samples taken from the same patient at different times.
  • With Svfor3/Svrev, every patient had at least one positive biopsy. Patients 2, 6 and 8 were positive in all three biopsies, Patients 1, 3 and 5 in two, and Patient 7 in one of three.
  • With Sv8/Sv9, Patients 7 and 8 were positive in all three biopsies and Patients 5 and 6 in two of three. Patient 3 was positive in one of the two samples that could be tested. Patient 1 was negative in all three. The text does not state Patient 2's result with these primers.
• The authors' conclusion: The authors concluded that SV40-like sequences are present in Australian malignant mesotheliomas. They wrote that it remains to be shown whether SV40 contributes significantly to malignant transformation, or whether mesothelioma provides an environment that favours viral replication in people with latent SV40 infection.
• Limitations the authors state:
  • The amplified products could be artefacts. They had not yet been confirmed by Southern analysis or by cloning and sequencing, which the authors planned for future work.
  • Contamination from the positive control cell line Met5A was considered as a possible explanation. The authors judged it unlikely.
  • Some negative biopsies may have contained mostly necrotic, fibrous or normal tissue, which would lower the sensitivity of the test.
  • The amplified sequences may come from an SV40-like or mutated virus rather than SV40 itself.
  • SV40 is closely similar to the BK and JC viruses that commonly infect humans, which complicates detection.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Mesothelioma, Oncogenesis, SV40.

Related studies

• No implication of Simian virus 40 in pathogenesis of malignant pleural mesothelioma in Slovenia — J. Hmeljak, I. Kern, et al. (2010)
• Human T cell responses to endogenously presented HLA-A*0201 restricted peptides of Simian virus 40 large T antigen — M.P. Velders, M.F. Macedo, et al. (2001)
• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)
• Simian virus 40 sequences in blood specimens from healthy individuals of Casale Monferrato, an industrial town with a history of asbestos pollution — C. Pancaldi, V. Balatti, et al. (2009)
• The presence of simian-virus 40 sequences in mesothelioma and mesothelial cells is associated with high levels of vascular endothelial growth factor — P. Cacciotti, L. Strizzi, et al. (2002)
• Progressive aberrant methylation of the RASSF1A gene in simian virus 40 infected human mesothelial cells — S. Toyooka, M. Carbone, et al. (2002)

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