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

Our plain-English summary of Mutations of p53 gene and SV40 sequences in asbestos associated and non-asbestos-associated mesotheliomas, by F.G. Mayall, G. Jacobson, R. Wilkins (Journal of Clinical Pathology, 1999).

The study

• Authors: F.G. Mayall, G. Jacobson, R. Wilkins
• Journal: Journal of Clinical Pathology
• Published: 1999;52(4):291-3
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Aim: To examine mesotheliomas for a possible relation between p53 immunostaining, p53 gene mutation, simian virus 40 (SV40), and asbestos exposure.

Methods: Paraffin 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 paraffin 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 differential 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 difference 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.

In plain English

This was a small laboratory study by researchers in Hamilton, New Zealand, using stored tissue from 11 mesotheliomas. The article does not say whether these were pleural or peritoneal. The authors tested each tumour for staining of the p53 protein, for mutations in part of the p53 gene, and for genetic material from simian virus 40 (SV40). A specialist centre in the UK counted asbestos fibres in lung tissue: crocidolite, amosite, tremolite and a type the table calls "chrysolite". Seven tumours were classed as asbestos associated. The other four included one case whose link to asbestos was uncertain, and the authors counted it as not asbestos associated. SV40 sequence was found in five of the seven asbestos-associated tumours and in none of the four others (p = 0.045, Fisher's exact test). p53 staining was seen in two of seven and three of four. The only p53 mutation, described as silent, was in the uncertain case. The p values for the p53 differences were 0.175 and 0.417. The authors concluded that this suggests a possible synergistic interaction between asbestos and SV40, and that a larger study is needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study of a small series of mesothelioma tissue samples (immunostaining, gene mutation analysis, virus DNA testing, and lung fibre counts)
• Who was studied: Paraffin tissue sections from 11 mesotheliomas, studied at Waikato Hospital and Waikato University, Hamilton, New Zealand. Dates and patient details are not given.
• Exposure: Asbestos exposure was judged from electron microscopic counts of crocidolite, amosite, tremolite and "chrysolite" fibres (million per gram of dried lung), done at Llandough Hospital, UK. SV40 virus sequences in the tumours were also studied.
• Main results:
  • SV40 sequence was detected in 5 of 7 asbestos-associated mesotheliomas and in none of the 4 other mesotheliomas.
  • Treating the uncertain case as not asbestos associated, the p values comparing the two groups were 0.175 for p53 immunostaining, 0.417 for p53 gene mutation, and 0.045 for SV40 (Fisher's exact test).
  • Among the 7 asbestos-associated cases, 2 showed p53 immunostaining and none had a p53 gene mutation.
  • Among the 4 other cases, 3 showed p53 immunostaining.
  • The only p53 gene mutation found was a silent one, in case 7, the case whose asbestos association was uncertain.
• The authors' conclusion: The authors concluded that they had shown a higher frequency of SV40 virus sequence in asbestos-associated mesotheliomas than in other mesotheliomas. They said this suggests a possible synergistic interaction between asbestos and SV40.
• Limitations the authors state:
  • The authors stated that a study with a larger number of cases is needed.
  • In one case the link to asbestos was uncertain because the asbestos level was only marginally raised. The authors' statistics assumed this case was not asbestos associated.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: SV40, Mesothelioma, Asbestos Exposure.

Related studies

• Crocidolite induces cell transformation and p53 gene mutation in BALB/c-3T3 cells — F. Lin, Y. Liu, et al. (2000)
• Absence of p53 mutations in malignant mesotheliomas — O. Mor, P. Yaron, et al. (1997)
• Analysis of K-ras and p53 mutations in mesotheliomas from humans and rats exposed to asbestos — Z. Ni, Y. Liu, et al. (2000)
• 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 — F. López-Ríos, P.B. Illei, et al. (2004)
• SV40-like DNA sequences in pleural mesothelioma, bronchopulmonary carcinoma, and non-malignant pulmonary diseases — F. Galateau-Salle, P. Bidet, et al. (1998)
• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)

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