Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity
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Published:2023-03-16
Issue:4
Volume:55
Page:607-618
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ISSN:1061-4036
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Container-title:Nature Genetics
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language:en
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Short-container-title:Nat Genet
Author:
Mangiante LiseORCID, Alcala NicolasORCID, Sexton-Oates Alexandra, Di Genova Alex, Gonzalez-Perez AbelORCID, Khandekar Azhar, Bergstrom Erik N., Kim JaeheeORCID, Liu Xiran, Blazquez-Encinas Ricardo, Giacobi Colin, Le Stang Nolwenn, Boyault SandrineORCID, Cuenin Cyrille, Tabone-Eglinger SeverineORCID, Damiola FrancescaORCID, Voegele Catherine, Ardin Maude, Michallet Marie-Cecile, Soudade Lorraine, Delhomme Tiffany M.ORCID, Poret Arnaud, Brevet Marie, Copin Marie-Christine, Giusiano-Courcambeck Sophie, Damotte Diane, Girard Cecile, Hofman Veronique, Hofman Paul, Mouroux Jérôme, Cohen Charlotte, Lacomme Stephanie, Mazieres Julien, de Montpreville Vincent Thomas, Perrin Corinne, Planchard Gaetane, Rousseau Nathalie, Rouquette Isabelle, Sagan Christine, Scherpereel Arnaud, Thivolet Francoise, Vignaud Jean-Michel, Jean Didier, Ilg Anabelle Gilg Soit, Olaso RobertORCID, Meyer Vincent, Boland-Auge AnneORCID, Deleuze Jean-FrancoisORCID, Altmuller Janine, Nuernberg Peter, Ibáñez-Costa AlejandroORCID, Castaño Justo P.ORCID, Lantuejoul Sylvie, Ghantous Akram, Maussion CharlesORCID, Courtiol Pierre, Hernandez-Vargas HectorORCID, Caux Christophe, Girard Nicolas, Lopez-Bigas NuriaORCID, Alexandrov Ludmil B., Galateau-Salle FrançoiseORCID, Foll MatthieuORCID, Fernandez-Cuesta LynnetteORCID
Abstract
AbstractMalignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that—in the case of the interdependent tumor cell morphology and adapted immune response—reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.
Publisher
Springer Science and Business Media LLC
Reference82 articles.
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