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Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications

Malignant pleural mesothelioma (MPM) is recognized as heterogeneous based both on histology and molecular profiling. Histology addresses inter-tumor and intra-tumor heterogeneity in MPM and describes three major types: epithelioid, sarcomatoid and biphasic, a combination of the former two types. Mol...

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Autores principales: Blum, Yuna, Meiller, Clément, Quetel, Lisa, Elarouci, Nabila, Ayadi, Mira, Tashtanbaeva, Danisa, Armenoult, Lucile, Montagne, François, Tranchant, Robin, Renier, Annie, de Koning, Leanne, Copin, Marie-Christine, Hofman, Paul, Hofman, Véronique, Porte, Henri, Le Pimpec-Barthes, Françoise, Zucman-Rossi, Jessica, Jaurand, Marie-Claude, de Reyniès, Aurélien, Jean, Didier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430832/
https://www.ncbi.nlm.nih.gov/pubmed/30902996
http://dx.doi.org/10.1038/s41467-019-09307-6
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author Blum, Yuna
Meiller, Clément
Quetel, Lisa
Elarouci, Nabila
Ayadi, Mira
Tashtanbaeva, Danisa
Armenoult, Lucile
Montagne, François
Tranchant, Robin
Renier, Annie
de Koning, Leanne
Copin, Marie-Christine
Hofman, Paul
Hofman, Véronique
Porte, Henri
Le Pimpec-Barthes, Françoise
Zucman-Rossi, Jessica
Jaurand, Marie-Claude
de Reyniès, Aurélien
Jean, Didier
author_facet Blum, Yuna
Meiller, Clément
Quetel, Lisa
Elarouci, Nabila
Ayadi, Mira
Tashtanbaeva, Danisa
Armenoult, Lucile
Montagne, François
Tranchant, Robin
Renier, Annie
de Koning, Leanne
Copin, Marie-Christine
Hofman, Paul
Hofman, Véronique
Porte, Henri
Le Pimpec-Barthes, Françoise
Zucman-Rossi, Jessica
Jaurand, Marie-Claude
de Reyniès, Aurélien
Jean, Didier
author_sort Blum, Yuna
collection PubMed
description Malignant pleural mesothelioma (MPM) is recognized as heterogeneous based both on histology and molecular profiling. Histology addresses inter-tumor and intra-tumor heterogeneity in MPM and describes three major types: epithelioid, sarcomatoid and biphasic, a combination of the former two types. Molecular profiling studies have not addressed intra-tumor heterogeneity in MPM to date. Here, we use a deconvolution approach and show that molecular gradients shed new light on the intra-tumor heterogeneity of MPM, leading to a reconsideration of MPM molecular classifications. We show that each tumor can be decomposed as a combination of epithelioid-like and sarcomatoid-like components whose proportions are highly associated with the prognosis. Moreover, we show that this more subtle way of characterizing MPM heterogeneity provides a better understanding of the underlying oncogenic pathways and the related epigenetic regulation and immune and stromal contexts. We discuss the implications of these findings for guiding therapeutic strategies, particularly immunotherapies and targeted therapies.
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spelling pubmed-64308322019-03-25 Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications Blum, Yuna Meiller, Clément Quetel, Lisa Elarouci, Nabila Ayadi, Mira Tashtanbaeva, Danisa Armenoult, Lucile Montagne, François Tranchant, Robin Renier, Annie de Koning, Leanne Copin, Marie-Christine Hofman, Paul Hofman, Véronique Porte, Henri Le Pimpec-Barthes, Françoise Zucman-Rossi, Jessica Jaurand, Marie-Claude de Reyniès, Aurélien Jean, Didier Nat Commun Article Malignant pleural mesothelioma (MPM) is recognized as heterogeneous based both on histology and molecular profiling. Histology addresses inter-tumor and intra-tumor heterogeneity in MPM and describes three major types: epithelioid, sarcomatoid and biphasic, a combination of the former two types. Molecular profiling studies have not addressed intra-tumor heterogeneity in MPM to date. Here, we use a deconvolution approach and show that molecular gradients shed new light on the intra-tumor heterogeneity of MPM, leading to a reconsideration of MPM molecular classifications. We show that each tumor can be decomposed as a combination of epithelioid-like and sarcomatoid-like components whose proportions are highly associated with the prognosis. Moreover, we show that this more subtle way of characterizing MPM heterogeneity provides a better understanding of the underlying oncogenic pathways and the related epigenetic regulation and immune and stromal contexts. We discuss the implications of these findings for guiding therapeutic strategies, particularly immunotherapies and targeted therapies. Nature Publishing Group UK 2019-03-22 /pmc/articles/PMC6430832/ /pubmed/30902996 http://dx.doi.org/10.1038/s41467-019-09307-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Blum, Yuna
Meiller, Clément
Quetel, Lisa
Elarouci, Nabila
Ayadi, Mira
Tashtanbaeva, Danisa
Armenoult, Lucile
Montagne, François
Tranchant, Robin
Renier, Annie
de Koning, Leanne
Copin, Marie-Christine
Hofman, Paul
Hofman, Véronique
Porte, Henri
Le Pimpec-Barthes, Françoise
Zucman-Rossi, Jessica
Jaurand, Marie-Claude
de Reyniès, Aurélien
Jean, Didier
Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications
title Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications
title_full Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications
title_fullStr Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications
title_full_unstemmed Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications
title_short Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications
title_sort dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430832/
https://www.ncbi.nlm.nih.gov/pubmed/30902996
http://dx.doi.org/10.1038/s41467-019-09307-6
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