Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity

Published on 16 March 2023 Updated on 16 January 2024

Malignant 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.

Author(s): Mangiante Lise, Alcala Nicolas, Sexton-Oates Alexandra, Di Genova Alex, Gonzalez-Perez Abel, Khandekar Azhar, Bergstrom Erik N, Kim Jaehee, Liu Xiran, Blazquez-Encinas Ricardo, Giacobi Colin, Le Stang Nolwenn, Boyault Sandrine, Cuenin Cyrille, Tabone-Eglinger Severine, Damiola Francesca, Voegele Catherine, Ardin Maude, Michallet Marie-Cecile, Soudade Lorraine, Delhomme Tiffany M, 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 Robert, Meyer Vincent, Boland-Auge Anne, Deleuze Jean-Francois, Altmuller Janine, Nuernberg Peter, Ibáñez-Costa Alejandro, Castaño Justo P, Lantuejoul Sylvie, Ghantous Akram, Maussion Charles, Courtiol Pierre, Hernandez-Vargas Hector, Caux Christophe, Girard Nicolas, Lopez-Bigas Nuria, Alexandrov Ludmil B, Galateau-Salle Françoise, Foll Matthieu, Fernandez-Cuesta Lynnette

Publishing year: 2023

Pages: 607-618