小柯机器人

法国国际癌症研究机构Lynnette Fernandez-Cuesta等研究人员合作发现，恶性胸膜间皮瘤的多组学分析确定驱动肿瘤间异质性的分子轴和专门的肿瘤图谱。2023年3月16日，《自然—遗传学》杂志在线发表了这一最新研究成果。

研究人员表示，恶性胸膜间皮瘤（MPM）是一种侵袭性癌症，其发病率不断上升，临床管理具有挑战性。

通过一系列大型的全基因组测序数据，并利用多组学因素分析与转录组和表观基因组数据相结合，研究人员证明目前世界卫生组织的分类只占患者间分子差异的10%。相反，MESOMICS项目为基于四个维度的MPM形态分子分类铺平了道路：倍性、肿瘤细胞形态学、适应性免疫反应和CpG岛甲基化谱。研究人员表明，这四个维度是互补的，抓住了病人之间的主要分子差异，并以极端的表型为界限，在相互依赖的肿瘤细胞形态和适应性免疫反应的情况下，反映了肿瘤的特化。这些发现揭示了MPM功能生物学和其基因组历史之间的相互作用，并为MPM患者临床行为中观察到的变化提供了见解。

附：英文原文

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

Author: 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, Jrme, 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, Ibez-Costa, Alejandro, Castao, 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, Franoise, Foll, Matthieu, Fernandez-Cuesta, Lynnette

Issue&Volume: 2023-03-16

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.

DOI: 10.1038/s41588-023-01321-1

Source: https://www.nature.com/articles/s41588-023-01321-1

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex