Evidence against a role for SV40 in human mesothelioma.
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.
Manfredi
James J
JJ
Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York, USA.
Dong
Jianli
J
Liu
Wen-jun
WJ
Resnick-Silverman
Lois
L
Qiao
Rui
R
Chahinian
Philippe
P
Saric
Marko
M
Gibbs
Allen R
AR
Phillips
James I
JI
Murray
J
J
Axten
Charles W
CW
Nolan
Robert P
RP
Aaronson
Stuart A
SA
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000096:biosynthesis / Q000235:genetics; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000821:virology; D008654:Mesothelioma / Q000235:genetics / Q000821:virology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000150:complications / Q000821:virology; D013539:Simian virus 40 / Q000235:genetics / Q000502:physiology*; D014412:Tumor Virus Infections / Q000150:complications / Q000821:virology
D000957:Antigens, Viral, Tumor; D004279:DNA, Viral