Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences

Our plain-English summary of Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences, by H.I. Pass, J.S. Donington, P. Wu, et al (The Journal of Thoracic and Cardiovascular Surgery, 1998).

The study

• Authors: H.I. Pass, J.S. Donington, P. Wu, P. Rizzo, M. Nishimura, R. Kennedy, M. Carbone
• Journal: The Journal of Thoracic and Cardiovascular Surgery
• Published: 1998;116(5):854-9
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: A cohort (20%) of patients with mesothelioma will not have an exposure to asbestos. Recently, a DNA tumor virus (simian virus 40) has been shown to cause hamster mesotheliomas; we previously described simian virus 40-like DNA amino terminus sequences in 29 of 48 mesotheliomas. We analyzed an additional 42 mesotheliomas to determine (1) whether our initial observations were durable and (2) the extent to which the simian virus 40 genome is present in mesotheliomas.

Methods: Genomic DNA was extracted from snap frozen mesothelioma tumor samples and from the simian virus 40-induced hamster mesothelioma tumor H9A. Polymerase chain reaction primers were used to amplify various simian virus 40 large T-antigen regions including a 105-base pair amino terminus fragment, a 281-base pair carboxyl terminus fragment, and a 310-base pair fragment of the enhancer promoter region. Endonuclease digestions and Southern blotting were used to verify the expected product.

Results: Thirty of the 42 (71%) samples amplified T-antigen amino sequences, and specificity was verified by Southern hybridization. Sixteen of 42 samples (38%) amplified the appropriate size fragment for the carboxyl terminus, and digestion with BsaB1 matched that of H9A. Twenty-two of 42 samples (52%) amplified simian virus 40 regulatory sequences and Fok1 digestion matched that of the hamster control tumor. Sequence analysis (4 patients) revealed 100% homology with the regulatory region of simian virus 40 strain 776.

Conclusions: These data suggest an association between the simian virus 40 virus and human mesothelioma that could be exploited for diagnostic/therapeutic options including early detection and potential vaccination strategies.

In plain English

This laboratory study looked for simian virus 40 (SV40) DNA in tumors from 42 consecutive cases of pleural and peritoneal mesothelioma. Tumors were frozen at surgery from March 1993 to May 1995. Using PCR, the authors tested three regions of the SV40 genome; an SV40-induced hamster mesothelioma was the positive control. A short segment of the large T antigen amino terminus was found in 30 of 42 tumors (71%) on gels, and, after probe hybridization, in 31 of 33; the article prints this as 92%, though 31 of 33 is about 94%. The carboxyl terminus was found in 16 of 42 (38%) and the regulatory region in 22 of 42 (52%). Overall, 24% had all three. In 4 patients, the regulatory region sequence was identical to the hamster control, derived from SV40 strain 776. The authors concluded the data suggest an association between SV40 and human mesothelioma. They stated that the study does not show the sequences' origin or implicate SV40 as a complete carcinogen. Citing their earlier study, they noted most of these patients have asbestos fibers in their lungs.

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 of human tumor tissue: PCR amplification of SV40 DNA regions, checked by Southern blotting, restriction enzyme digestion and, in 4 patients, sequencing; the authors' second series after an earlier report
• Who was studied: Tumor samples from 42 consecutive cases of pleural and peritoneal mesothelioma, snap frozen in the operating room from March 1993 to May 1995, from the National Cancer Institute mesothelioma tissue bank (United States)
• Exposure: The exposure examined was simian virus 40 (SV40) DNA in the tumors: the large T antigen amino terminus, the carboxyl terminus, and the regulatory (promoter/enhancer) region. Asbestos exposure was not measured or compared in this report.
• Main results:
  • 105-bp T antigen amino terminus segment: found in 30 of 42 tumors (71%) on ethidium bromide gels. After hybridizing with a specific probe it was found in 31 of 33, which the article prints as 92%; 31 of 33 works out to about 94%, and the article does not explain the discrepancy.
  • Larger amino terminus region (SVfor2 primers): 25% amplification rate on Southern blot
  • T antigen carboxyl terminus: found in 16 of 42 tumors (38%). The BsaB1 digestion pattern was identical to the hamster mesothelioma control.
  • SV40 regulatory region: amplified in 22 of 42 tumors (52%). The Fok1 digestion pattern was identical to the hamster control.
  • In 4 patients, the sequenced regulatory region was identical to the hamster mesothelioma control, which was derived from wild type SV40 strain 776
  • 24% of the mesotheliomas had amplification of all 3 regions
• The authors' conclusion: The authors concluded that the data suggest an association between SV40 and human mesothelioma that could be used for diagnosis or treatment, including early detection and possible vaccination. They also stated that the data substantiate that SV40 sequences are consistently present in mesothelioma.
• Limitations the authors state:
  • The study does not show where the sequences came from and does not implicate SV40 as a complete carcinogen in mesothelioma
  • Citing their previous study, the authors noted that most of these patients have asbestos fibers in their lungs
  • In the published discussion, the lead author said SV40 status had not been analyzed by asbestos level, and that SV40 could not be said to do anything independently of an asbestos background

Topics

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

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

Related studies

• Simian virus 40 is present in most United States human mesotheliomas, but it is rarely present in non-Hodgkin's lymphoma — P. Rizzo, M. Carbone, et al. (1999)
• Simian virus 40 large T antigen (SV40LTAg) primer specific DNA amplification in human pleural mesothelioma tissue — C. Pepper, B. Jasani, et al. (1996)
• 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)
• New molecular and epidemiological issues in mesothelioma: role of SV40 — M. Carbone, S. Fisher, et al. (1999)
• Simian virus-40 large-T antigen binds p53 in human mesotheliomas — M. Carbone, P. Rizzo, et al. (1997)
• Asbestos, Simian virus 40 and malignant mesothelioma — S.C. Stenton (1997)

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