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

89 Citations (Scopus)

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

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Polyomavirus Transforming Antigens
Viral Tumor Antigens
Mesothelioma
Cell Line
Neoplasms
Oncogene Proteins
Formaldehyde
DNA Damage
Haplorhini
Kidney
Polymerase Chain Reaction
Antibodies
DNA
Infection
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Manfredi, J. J., Dong, J., Liu, W. J., Resnick-Silverman, L., Qiao, R., Chahinian, 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

Evidence against a role for SV40 in human mesothelioma. / Manfredi, James J.; Dong, Jianli; Liu, Wen Jun; Resnick-Silverman, Lois; Qiao, Rui; Chahinian, Philippe; Saric, Marko; Gibbs, Allen R.; Phillips, James I.; Murray, J.; Axten, Charles W.; Nolan, Robert P.; Aaronson, Stuart A.

In: Cancer Research, Vol. 65, No. 7, 01.04.2005, p. 2602-2609.

Research output: Contribution to journalArticle

Manfredi, JJ, Dong, J, Liu, WJ, Resnick-Silverman, L, Qiao, R, Chahinian, P, Saric, M, Gibbs, AR, Phillips, JI, Murray, J, Axten, CW, Nolan, RP & Aaronson, SA 2005, 'Evidence against a role for SV40 in human mesothelioma', Cancer Research, vol. 65, no. 7, pp. 2602-2609. https://doi.org/10.1158/0008-5472.CAN-04-2461
Manfredi JJ, Dong J, Liu WJ, Resnick-Silverman L, Qiao R, Chahinian P et al. Evidence against a role for SV40 in human mesothelioma. Cancer Research. 2005 Apr 1;65(7):2602-2609. https://doi.org/10.1158/0008-5472.CAN-04-2461
Manfredi, James J. ; Dong, Jianli ; Liu, Wen Jun ; Resnick-Silverman, Lois ; Qiao, Rui ; Chahinian, Philippe ; Saric, Marko ; Gibbs, Allen R. ; Phillips, James I. ; Murray, J. ; Axten, Charles W. ; Nolan, Robert P. ; Aaronson, Stuart A. / Evidence against a role for SV40 in human mesothelioma. In: Cancer Research. 2005 ; Vol. 65, No. 7. pp. 2602-2609.
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