Telomerase activity in human pleural mesothelioma

Our plain-English summary of Telomerase activity in human pleural mesothelioma, by K. Dhaene, R. Hübner, S. Kumar-Singh, et al (Thorax, 1998).

The study

• Authors: K. Dhaene, R. Hübner, S. Kumar-Singh, B. Weyn, E. Van Marck
• Journal: Thorax
• Published: 1998;53(11):915-8
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Gradual telomere erosion eventually limits the replicative life span of somatic cells and is regarded as an ultimate tumour suppressor mechanism, eliminating cells that have accumulated genetic alterations. Telomerase, which has been found in over 85% of human cancers, elongates telomeres and may be required for tumorigenesis by the process of immortalisation. Malignant mesothelioma is an incurable malignancy with a poor prognosis. The disease becomes symptomatic decades after exposure to carcinogenic asbestos fibres, suggesting the long term survival of pre-malignant cell clones. This study investigated the presence of telomerase in pleural malignant mesothelioma, which may be the target for future anti-telomerase drugs.

Methods: Telomerase activity was semiquantitatively measured in extracts from 22 primary pleural mesotheliomas, two benign solitary fibrous tumours of the pleura, four mesothelioma cell lines, and six short term mesothelial cell cultures from normal pleura using a non-isotopic dilution assay of the telomeric repeat amplification protocol.

Results: Twenty of the 22 primary mesotheliomas (91%) and all tumour derived mesothelioma cell lines were telomerase positive. Different levels of enzyme activity were observed in the tumours of different histological subtypes. Telomerase activity could not be detected in the six normal mesothelial cell cultures or in the two mesotheliomas. Both benign solitary fibrous tumours showed strong telomerase activity.

Conclusions: Telomerase activity is found in a high proportion of mesotheliomas and anti-telomerase drugs might therefore be useful clinically. The results are consistent with the hypothesis that telomerase activity may be a feature of carcinogenesis in mesotheliomas and possibly in many other cancers.

In plain English

This was a small laboratory study from the Department of Pathology at the University of Antwerp, Belgium. The authors tested for activity of telomerase, an enzyme that lengthens the ends of chromosomes. They tested tissue from 22 pleural mesotheliomas (nine epithelial, four sarcomatous, nine mixed), two benign solitary fibrous tumours of the pleura, four mesothelioma cell lines, and six cultures of normal mesothelial cells taken at autopsy from people without cancer. Telomerase activity was found in 20 of the 22 mesotheliomas (91%), in all four cell lines and in both benign tumours. In dilution tests, five of the 20 positive mesotheliomas still showed activity after tenfold dilution and two after hundredfold dilution, which the authors read as high levels. Both benign tumours also showed high levels. No activity was found in the normal mesothelial cells or in two mesotheliomas. The study did not measure asbestos exposure. The authors concluded that telomerase activity is found in a high proportion of mesotheliomas and that anti-telomerase drugs might therefore be useful clinically. They noted that the study was too small for statistical analysis and that larger series are 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 (rapid communication) measuring telomerase activity in tumour tissue, cell lines and normal cell cultures using a semiquantitative dilution TRAP assay
• Who was studied: 22 pleural mesotheliomas (nine epithelial, four sarcomatous, nine mixed) and two benign solitary fibrous tumours of the pleura, sampled at pleuroscopy; four mesothelioma cell lines (UIA-MM 1, 2, 5 and 7) isolated from pleural fluid; and short term mesothelial cell cultures from the pleura of necropsied non-cancerous patients (six, per the abstract). The work was done at the Department of Pathology, University of Antwerp, Belgium. No study dates are given.
• Exposure: Not studied. The article mentions asbestos only as background and did not assess the patients' asbestos exposure.
• Main results:
  • Telomerase activity was detected in 20 of 22 mesotheliomas (91%), in all four mesothelioma cell lines, and in both solitary fibrous tumours (tested with 6 µg protein extracts).
  • Of the 20 telomerase positive mesotheliomas, five retained signals after 10-fold dilution and two retained signals after 100-fold dilution, which the authors interpreted as high levels of telomerase activity.
  • No telomerase activity was detected in the normal mesothelial cells or in two mesotheliomas (MM2 and MM21). The authors excluded false negatives caused by Taq polymerase inhibitors, because control products were amplified in all assays.
  • Both benign solitary fibrous tumours showed high levels of activity after 10-fold and 100-fold dilution of their extracts.
• The authors' conclusion: The authors concluded that telomerase activity is found in a high proportion of mesotheliomas and that anti-telomerase drugs might therefore be useful clinically.
• Limitations the authors state:
  • The study was small, so no statistical analysis was performed. This included any test of a link between telomerase level and histological subtype.
  • The authors stated that statistical analysis may be inaccurate because of weaknesses in the TRAP assay, which loses tumour heterogeneity and tissue structure.
  • Because two mesotheliomas were telomerase negative, the authors could not exclude that some mesotheliomas use telomerase-independent mechanisms or are not immortal. They said this would weaken the efficacy of future anti-telomerase drugs.
  • The authors stated that larger series need to be studied.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Tumorigenesis, Malignant Mesothelioma, Prognosis, Carcinogenic, Pleura, Mesothelioma, Mesothelial Cells.

Related studies

• SV40 infection induces telomerase activity in human mesothelial cells — R. Foddis, A. De Rienzo, et al. (2002)
• Telomerase activity analyzed with TRAP in situ provides additional information in effusions remaining equivocal after immunocytochemistry and hyaluronan analysis — E. Adell, A. Dejmek (2014)
• Telomerase activity in pleural malignant mesotheliomas — A.Y. Au, T. Hackl, et al. (2011)
• Telomeres and telomerase in mesothelioma: Pathophysiology, biomarkers and emerging therapeutic strategies (Review) — D. Andreikos, D.A. Spandidos, et al. (2025)
• Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine — S. Thunold, E. Hernes, et al. (2025)
• Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases — A. Mervic, K. Goricar, et al. (2024)

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