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Evaluation of clonal origin of malignant mesothelioma

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 malign...

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Autores principales: Comertpay, Sabahattin, Pastorino, Sandra, Tanji, Mika, Mezzapelle, Rosanna, Strianese, Oriana, Napolitano, Andrea, Baumann, Francine, Weigel, Tracey, Friedberg, Joseph, Sugarbaker, Paul, Krausz, Thomas, Wang, Ena, Powers, Amy, Gaudino, Giovanni, Kanodia, Shreya, Pass, Harvey I, Parsons, Barbara L, Yang, Haining, Carbone, Michele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255423/
https://www.ncbi.nlm.nih.gov/pubmed/25471750
http://dx.doi.org/10.1186/s12967-014-0301-3
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author Comertpay, Sabahattin
Pastorino, Sandra
Tanji, Mika
Mezzapelle, Rosanna
Strianese, Oriana
Napolitano, Andrea
Baumann, Francine
Weigel, Tracey
Friedberg, Joseph
Sugarbaker, Paul
Krausz, Thomas
Wang, Ena
Powers, Amy
Gaudino, Giovanni
Kanodia, Shreya
Pass, Harvey I
Parsons, Barbara L
Yang, Haining
Carbone, Michele
author_facet Comertpay, Sabahattin
Pastorino, Sandra
Tanji, Mika
Mezzapelle, Rosanna
Strianese, Oriana
Napolitano, Andrea
Baumann, Francine
Weigel, Tracey
Friedberg, Joseph
Sugarbaker, Paul
Krausz, Thomas
Wang, Ena
Powers, Amy
Gaudino, Giovanni
Kanodia, Shreya
Pass, Harvey I
Parsons, Barbara L
Yang, Haining
Carbone, Michele
author_sort Comertpay, Sabahattin
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-014-0301-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-42554232014-12-05 Evaluation of clonal origin of malignant mesothelioma Comertpay, Sabahattin Pastorino, Sandra Tanji, Mika Mezzapelle, Rosanna Strianese, Oriana Napolitano, Andrea Baumann, Francine Weigel, Tracey Friedberg, Joseph Sugarbaker, Paul Krausz, Thomas Wang, Ena Powers, Amy Gaudino, Giovanni Kanodia, Shreya Pass, Harvey I Parsons, Barbara L Yang, Haining Carbone, Michele J Transl Med Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-014-0301-3) contains supplementary material, which is available to authorized users. BioMed Central 2014-12-04 /pmc/articles/PMC4255423/ /pubmed/25471750 http://dx.doi.org/10.1186/s12967-014-0301-3 Text en © Comertpay et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Comertpay, Sabahattin
Pastorino, Sandra
Tanji, Mika
Mezzapelle, Rosanna
Strianese, Oriana
Napolitano, Andrea
Baumann, Francine
Weigel, Tracey
Friedberg, Joseph
Sugarbaker, Paul
Krausz, Thomas
Wang, Ena
Powers, Amy
Gaudino, Giovanni
Kanodia, Shreya
Pass, Harvey I
Parsons, Barbara L
Yang, Haining
Carbone, Michele
Evaluation of clonal origin of malignant mesothelioma
title Evaluation of clonal origin of malignant mesothelioma
title_full Evaluation of clonal origin of malignant mesothelioma
title_fullStr Evaluation of clonal origin of malignant mesothelioma
title_full_unstemmed Evaluation of clonal origin of malignant mesothelioma
title_short Evaluation of clonal origin of malignant mesothelioma
title_sort evaluation of clonal origin of malignant mesothelioma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255423/
https://www.ncbi.nlm.nih.gov/pubmed/25471750
http://dx.doi.org/10.1186/s12967-014-0301-3
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