Evaluation of clonal origin of malignant mesothelioma

Sabahattin Comertpay, Sandra Pastorino, Mika Tanji, Rosanna Mezzapelle, Oriana Strianese, Andrea Napolitano, Francine Baumann, Tracey Weigel, Joseph Friedberg, Paul Sugarbaker, Thomas Krausz, Ena Wang, Amy Powers, Giovanni Gaudino, Shreya Kanodia, Harvey I. Pass, Barbara L. Parsons, Haining Yang, Michele Carbone

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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.

Original languageEnglish
Article number301
JournalJournal of translational medicine
Issue number1
Publication statusPublished - 4 Dec 2014


  • Carcinogenesis
  • Clonal origin
  • HUMARA assay
  • Malignant mesothelioma
  • Polyclonal tumors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Comertpay, S., Pastorino, S., Tanji, M., Mezzapelle, R., Strianese, O., Napolitano, A., Baumann, F., Weigel, T., Friedberg, J., Sugarbaker, P., Krausz, T., Wang, E., Powers, A., Gaudino, G., Kanodia, S., Pass, H. I., Parsons, B. L., Yang, H., & Carbone, M. (2014). Evaluation of clonal origin of malignant mesothelioma. Journal of translational medicine, 12(1), [301]. https://doi.org/10.1186/s12967-014-0301-3