Evaluation of clonal origin of malignant mesothelioma

Our plain-English summary of Evaluation of clonal origin of malignant mesothelioma, by S. Comertpay, S. Pastorino, M. Tanji, et al (Journal of Translational Medicine, 2014).

The study

• Authors: S. Comertpay, S. Pastorino, M. Tanji, R. Mezzapelle, O. Strianese, A. Napolitano, F. Baumann, T. Weigel, J. Friedberg, P. Sugarbaker, T. Krausz, E. Wang, A. Powers, G. Gaudino, S. Kanodia, H.I. Pass, B.L. Parsons, H. Yang, M. Carbone
• Journal: Journal of Translational Medicine
• Published: 2014;12:301
• Cited by: 73 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The hypothesis that most cancers are of monoclonal origin is often accepted as a fact in the scientific community. This dogma arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas, which originate as monoclonal tumors. The possible clonal origin of malignant mesothelioma (MM) has not been investigated. Asbestos inhalation induces a chronic inflammatory response at sites of fiber deposition that may lead to malignant transformation after 30-50 years latency. As many mesothelial cells are simultaneously exposed to asbestos fibers and to asbestos-induced inflammation, it may be possible that more than one cell undergoes malignant transformation during the process that gives rise to MM, and result in a polyclonal malignancy.

Methods And Results: To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 16 biopsies from 14 women MM patients. Out of 16 samples, one was non-informative due to skewed Lyonization in its normal adjacent tissue. Fourteen out of the 15 informative samples revealed two electrophoretically distinct methylated HUMARA alleles, the Corrected Allele Ratio (CR) calculated on the allele peak areas indicating polyclonal origin MM.

Conclusions: Our results show that MM originate as polyclonal tumors and suggest that the carcinogenic "field effect" of mineral fibers leads to several premalignant clones that give rise to these polyclonal malignancies.

In plain English

This laboratory study asked whether malignant mesothelioma tumors grow from a single cell (monoclonal) or from several cells (polyclonal). The authors used the HUMARA assay. This DNA test tracks which X chromosome is switched off in tumor cells, so it works only on tissue from women. They tested 16 frozen tumor biopsies, stage I to III, from 14 women whose samples were collected at four US surgical centers. In 2 of the women, two separate nodules from the same pleura were tested. The tumors were epithelioid or biphasic. No sarcomatoid tumors were available. The study did not measure asbestos exposure. One of the 16 samples could not be interpreted. Of the 15 interpretable samples, 14 (93.33%, 95% confidence interval 68.16% to 100%) showed a polyclonal pattern. In one woman, one nodule showed a monoclonal pattern and the other a polyclonal one. The authors concluded that mesothelioma arises as polyclonal tumors. They suggested this may reflect a carcinogenic "field effect" of mineral fibers. They noted that the test cannot be used on tumors from men and that sarcomatoid mesothelioma remains to be tested.

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 tumor clonality, using the HUMARA (X-chromosome inactivation) assay on DNA from surgically removed tumor tissue and nearby normal tissue
• Who was studied: 16 frozen malignant mesothelioma biopsies, stage I to III, from 14 women. Samples were collected at New York University, MedStar Washington Hospital Center, University of Wisconsin and Penn Presbyterian Medical Center, and analyzed at the University of Hawaii Cancer Center. In 2 of the 14 women, two distinct nodules from the same pleura were tested. Tumors were epithelioid or biphasic.
• Exposure: Not measured. The article does not report asbestos exposure histories or fiber types for these patients.
• Main results:
  • 15 of the 16 biopsies gave interpretable results. One sample (L-III-18, described as familial mesothelioma) was non-informative.
  • Among the 15 informative samples, 14 showed a polyclonal pattern: 93.33% (14/15), 95% confidence interval 68.16% to 100%. The authors stated this did not differ significantly from 100%.
  • In one patient (case 524), one nodule (524B) showed a monoclonal pattern (CR = 0.19) while the other nodule (524A) was polyclonal (CR = 0.36)
  • In control tests, the assay detected the less frequent allele when it made up at least 1/8 (12.5%) of the input DNA
• The authors' conclusion: The authors concluded that malignant mesothelioma arises as polyclonal tumors. They suggested that the carcinogenic "field effect" of mineral fibers leads to several premalignant clones.
• Limitations the authors state:
  • The assay can be used only on tumors from women, so no tumors from men were studied
  • Sarcomatoid mesotheliomas were not tested because specimens were not available

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Monoclonal, Sarcoma, Deposition, Malignant Transformation, Latency, Mesothelial Cells, Inflammation.

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