Mutations of p53 gene and SV40 sequences in asbestos associated and non-asbestos-associated mesotheliomas.

Abstract

Aim-To examine mesotheliomas for a possible relation between p53 immunostaining, p53 gene mutation, simian virus 40 (SV40), and asbestos exposure. Methods-ParaYn sections from 11 mesotheliomas were used for p53 immunostaining and also to extract DNA. This was analysed for the presence of mutations in exons 5 to 8 of the p53 gene using a "cold" single strand conformational polymorphism method, together with sequencing. The DNA from the paraYn sections was also used to search for SV40 sequences. A 105 base pair segment at the 3' of the SV40 large T antigen (Tag) was targeted and any PCR amplification products were sequenced to confirm that they were of SV40 origin. EDAX electron microscopic diVerential mineral fibre counts were performed on dried lung tissue at a specialist referral centre. Results-The fibre counts showed that seven of the mesotheliomas were associated with abnormally high asbestos exposure. Of these, two showed p53 immunostaining, none showed p53 gene mutation, and five showed SV40. Of the four other mesotheliomas, three showed p53 immunostaining, one showed a (silent) p53 mutation, and none showed SV40. The diVerence in frequency of SV40 detection was significant at the p < 0.05 level. Conclusions-Immunostaining for the p53 gene was relatively common but p53 mutations were rare in this series. SV40 virus sequence was detected in five of seven asbestos associated mesotheliomas but in none of the non-asbestos-associated mesotheliomas. This suggests there may be a synergistic interaction between asbestos and SV40 in human mesotheliomas. A study with a larger number of cases is needed to investigate these observations further. (J Clin Pathol 1999;52:291-293)

SV40 replication in human mesothelial cells induces HGF/Met receptor activation: A model for viral-related carcinogenesis of human malignant mesothelioma

“…The direct involvement of SV40 Tag expression in the growth of malignant mesothelioma cells has been described (8), and SV40 is associated with a shorter survival of MM patients (9). A synergistic action between SV40 and asbestos fibers has been suggested (10), and HMC have been shown to be highly sensitive to SV40-mediated transformation (11).…”

Association of SV40 with human tumors

“…None of the non-asbestos associated mesotheliomas were positive for SV40. Mayall suggested the possibility of a synergistic relationship between SV40 and asbestos in the development of malignant mesothelioma (Mayall et al, 1999).…”

Assessment of the Mutations of p53 Suppressor Gene and Ha- and Ki-ras Oncogenes in Malignant Mesothelioma in Relation to Asbestos Exposure: A Study of 12 American Patients.

“…Only one mutation in the p53 suppressor gene has been found in fifteen malignant mesothelioma patients, a GGA TGA transversion in codon 266 (Exon 8) 6) . Also, one silent mutation has been observed in the p53 suppressor gene of eleven primary malignant mesothelioma patients 7) . In other studies, no alteration in the Ha-ras oncogene was found in eleven primary tumors of malignant mesothelioma including those from cases with asbestos exposure 8) , and no alteration in the p53 suppressor gene was demonstrated in thirteen primary tumors of malignant mesothelioma, of which only two cases had a history of asbestos exposure 9) .…”