SV40 as a causative agent in mesothelioma: a new twist to the story
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Wellcome Advanced Fellow, University College London and Honorary Chest Physician, Osler Chest Unit, Oxford, UK; ycgarylee@hotmail.com
Lopez-Rios F, Illei PB, Rusch V, Ladanyi M. Evidence against a role for SV40 infection in human mesotheliomas and high risk of false-positive PCR results owing to presence of SV40 sequences in common laboratory plasmids. Lancet 2004;364:1157–66
The potential causal role of simian virus 40 (SV40) in tumourigenesis is the most contentious issue in mesothelioma research of recent years. SV40 is a potent tumour virus and can induce mesothelioma in experimental animals. However, clinical evidence linking SV40 with mesothelioma remains inconclusive. SV40 has been reported in human mesothelioma tissues in many, but not all, previous publications. Although the criteria for causality have not been satisfied, strategies targeting SV40 are already being pursued in clinical trials for mesothelioma.
Lopez-Rios et al used several lines of approach to show that PCR primers used to detect SV40 in many other studies were targeting sequences within the SV40 genome that are also present in common laboratory plasmids. "Positive" SV40 detection in the mesothelioma samples was actually amplication of the DNA of laboratory plasmids rather than that of SV40. Using carefully designed primers to avoid false positives from plasmid contamination, they confirmed that DNA of the SV40 T antigen was not present in 71 mesothelioma samples. To further prove the point, they showed that neither the RNA (by RT-PCR) nor protein (by immunohistochemistry) of SV40 T antigen were detectable in any of the 71 samples. The data strongly suggest that previous reports of SV40 in mesothelioma were the result of laboratory contamination rather than genuine viral infection of the human tissue.
The methodology of this paper appears robust and its results seriously question the evidence upon which proponents of SV40 base the causality theory. There is little doubt that it will spark a new round of debate on SV40 and mesothelioma.(Y C G Lee)
Lopez-Rios F, Illei PB, Rusch V, Ladanyi M. Evidence against a role for SV40 infection in human mesotheliomas and high risk of false-positive PCR results owing to presence of SV40 sequences in common laboratory plasmids. Lancet 2004;364:1157–66
The potential causal role of simian virus 40 (SV40) in tumourigenesis is the most contentious issue in mesothelioma research of recent years. SV40 is a potent tumour virus and can induce mesothelioma in experimental animals. However, clinical evidence linking SV40 with mesothelioma remains inconclusive. SV40 has been reported in human mesothelioma tissues in many, but not all, previous publications. Although the criteria for causality have not been satisfied, strategies targeting SV40 are already being pursued in clinical trials for mesothelioma.
Lopez-Rios et al used several lines of approach to show that PCR primers used to detect SV40 in many other studies were targeting sequences within the SV40 genome that are also present in common laboratory plasmids. "Positive" SV40 detection in the mesothelioma samples was actually amplication of the DNA of laboratory plasmids rather than that of SV40. Using carefully designed primers to avoid false positives from plasmid contamination, they confirmed that DNA of the SV40 T antigen was not present in 71 mesothelioma samples. To further prove the point, they showed that neither the RNA (by RT-PCR) nor protein (by immunohistochemistry) of SV40 T antigen were detectable in any of the 71 samples. The data strongly suggest that previous reports of SV40 in mesothelioma were the result of laboratory contamination rather than genuine viral infection of the human tissue.
The methodology of this paper appears robust and its results seriously question the evidence upon which proponents of SV40 base the causality theory. There is little doubt that it will spark a new round of debate on SV40 and mesothelioma.(Y C G Lee)