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Evidence against a Role for SV40 in Human Mesothelioma

¹ Department of Oncological Sciences, Mount Sinai School of Medicine; ² Center for Applied Studies of The Environment and Earth and Environmental Sciences of the Graduate School and University Center of The City University of New York, New York, New York; ³ Institute for Medical Research and Occupational Health, Zagreb, Croatia; ⁴ Llandough Hospital, Pernarth, United Kingdom; and ⁵ National Institute for Occupational Health and the School of Public Health, University of Witswatersrand, Johannesburg, Republic of South Africa

Requests for reprints: Stuart A. Aaronson, Mt. Sinai Medical Center, One Gustave Levy Place, New York, NY 10020. Phone: 212-659-5400; Fax: 212-987-2240; E-mail: stuart.aaronson{at}mssm.edu.

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.

Key Words: mesothelioma • SV40 • large T antigen • p53 • DNA tumor viruses

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