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| Item Type: | Article |
|---|---|
| Title: | Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity |
| Creators Name: | Mangiante, L. and Alcala, N. and Sexton-Oates, A. and Di Genova, A. and Gonzalez-Perez, A. and Khandekar, A. and Bergstrom, E.N. and Kim, J. and Liu, X. and Blazquez-Encinas, R. and Giacobi, C. and Le Stang, N. and Boyault, S. and Cuenin, C. and Tabone-Eglinger, S. and Damiola, F. and Voegele, C. and Ardin, M. and Michallet, M.C. and Soudade, L. and Delhomme, T.M. and Poret, A. and Brevet, M. and Copin, M.C. and Giusiano-Courcambeck, S. and Damotte, D. and Girard, C. and Hofman, V. and Hofman, P. and Mouroux, J. and Cohen, C. and Lacomme, S. and Mazieres, J. and de Montpreville, V.T. and Perrin, C. and Planchard, G. and Rousseau, N. and Rouquette, I. and Sagan, C. and Scherpereel, A. and Thivolet, F. and Vignaud, J.M. and Jean, D. and Ilg, A.G.S. and Olaso, R. and Meyer, V. and Boland-Auge, A. and Deleuze, J.F. and Altmuller, J. and Nuernberg, P. and Ibáñez-Costa, A. and Castaño, J.P. and Lantuejoul, S. and Ghantous, A. and Maussion, C. and Courtiol, P. and Hernandez-Vargas, H. and Caux, C. and Girard, N. and Lopez-Bigas, N. and Alexandrov, L.B. and Galateau-Salle, F. and Foll, M. and Fernandez-Cuesta, L. |
| Abstract: | 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. |
| Keywords: | Lung Neoplasms, Malignant Mesothelioma, Mesothelioma, Multiomics, Pleural Neoplasms, Tumor Biomarkers |
| Source: | Nature Genetics |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Volume: | 55 |
| Number: | 4 |
| Page Range: | 607-618 |
| Date: | April 2023 |
| Official Publication: | https://doi.org/10.1038/s41588-023-01321-1 |
| PubMed: | View item in PubMed |
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