Evidence against a role for SV40 in human mesothelioma

James J. Manfredi, Jianli Dong, Wen Jun Liu, Lois Resnick-Silverman, Rui Qiao, Philippe Chahinian, Marko Saric, Allen R. Gibbs, James I. Phillips, J. Murray, Charles W. Axten, Robert P. Nolan, Stuart A. Aaronson

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

SV40 has been implicated in the etiology of 40% to 60% of human mesotheliomas. These studies could have important medical implications concerning possible sources of human infection and potential therapies if human tumors are induced by this agent. We did PCR-based analysis to detect SV40 large T antigen DNA in human mesotheliomas. None of 69 tumors in which a single copy gene was readily amplified contained detectable SV40 large T antigen sequences. Under these conditions, it was possible to detect one copy of integrated SV40 DNA per cell in a mixture containing a 5,000-fold excess of normal cells using formalin-fixed preparations. Kidney, a known reservoir of SV40 in monkeys, from some of these individuals were also negative for SV40 large T antigen sequences. A subset of mesotheliomas was analyzed for SV40 large T antigen expression by immunostaining with a highly specific SV40 antibody. These tumors as well as several human mesothelioma cell lines previously reported to contain SV40 large T antigen were negative for detection of the virally encoded oncoprotein. Moreover, mesothelioma cell lines with wild-type p53 showed normal p53 function in response to genotoxic stress, findings inconsistent with p53 inactivation by the putative presence of SV40 large T antigen. Taken together, these findings strongly argue against a role of SV40 by any known transformation mechanism in the etiology of the majority of human malignant mesotheliomas.

Original languageEnglish (US)
Pages (from-to)2602-2609
Number of pages8
JournalCancer Research
Volume65
Issue number7
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Manfredi, J. J., Dong, J., Liu, W. J., Resnick-Silverman, L., Qiao, R., Chahinian, P., Saric, M., Gibbs, A. R., Phillips, J. I., Murray, J., Axten, C. W., Nolan, R. P., & Aaronson, S. A. (2005). Evidence against a role for SV40 in human mesothelioma. Cancer Research, 65(7), 2602-2609. https://doi.org/10.1158/0008-5472.CAN-04-2461