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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Yuna Blum, Clément Meiller, Lisa Quetel, Nabila Elarouci, Mira Ayadi, Danisa Tashtanbaeva, Lucile Armenoult, François Montagne, Robin Tranchant, Annie Renier, Leanne de Koning, Marie-Christine Copin, Paul Hofman, Véronique Hofman, Henri Porte, Françoise Le Pimpec-Barthes, Jessica Zucman-Rossi, Marie-Claude Jaurand, Aurélien de Reyniès, Didier Jean

ABSTRACT

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. More... »

PAGES

1333

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-019-09307-6

DOI

http://dx.doi.org/10.1038/s41467-019-09307-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112944409

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30902996


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