Genetic alterations of malignant pleural mesothelioma: association with tumor heterogeneity and overall survival
| العنوان: | Genetic alterations of malignant pleural mesothelioma: association with tumor heterogeneity and overall survival |
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| المؤلفون: | Stefano Caruso, Yuna Blum, Lisa Quetel, Sandrine Imbeaud, Véronique Hofman, Arnaud Scherpereel, Laure Gibault, Ecaterina Pintilie, Françoise Le Pimpec-Barthes, Jessica Zucman-Rossi, Clément Meiller, François Montagne, Julien de Wolf, Didier Jean, Cécile Badoual, Paul Hofman, Jean-Baptiste Assié, Marie-Christine Copin, Isabelle Monnet, Marie-Claude Jaurand, Robin Tranchant |
| المصدر: | Molecular Oncology Molecular Oncology, Vol 14, Iss 6, Pp 1207-1223 (2020) |
| بيانات النشر: | John Wiley and Sons Inc., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Adult, Male, Cancer Research, Mutation rate, Pleural Neoplasms, Locus (genetics), Kaplan-Meier Estimate, Gene mutation, Biology, Tumor heterogeneity, lcsh:RC254-282, 03 medical and health sciences, Genetic Heterogeneity, Young Adult, 0302 clinical medicine, thoracic cancer, SETD2, Cell Line, Tumor, tumor heterogeneity, Genetics, Humans, Gene, Research Articles, gene mutations, Aged, Aged, 80 and over, BAP1, tumor molecular classification, Mesothelioma, Malignant, General Medicine, Middle Aged, Precision medicine, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Survival Analysis, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Mutation, Cancer research, Molecular Medicine, Female, prognosis, Research Article |
| الوصف: | Development of precision medicine for malignant pleural mesothelioma (MPM) requires a deep knowledge of tumor heterogeneity. Histologic and molecular classifications and histo‐molecular gradients have been proposed to describe heterogeneity, but a deeper understanding of gene mutations in the context of MPM heterogeneity is required and the associations between mutations and clinical data need to be refined. We characterized genetic alterations on one of the largest MPM series (266 tumor samples), well annotated with histologic, molecular and clinical data of patients. Targeted next‐generation sequencing was performed focusing on the major MPM mutated genes and the TERT promoter. Molecular heterogeneity was characterized using predictors allowing classification of each tumor into the previously described molecular subtypes and the determination of the proportion of epithelioid‐like and sarcomatoid‐like components (E/S.scores). The mutation frequencies are consistent with literature data, but this study emphasized that TERT promoter, not considered by previous large sequencing studies, was the third locus most affected by mutations in MPM. Mutations in TERT promoter, NF2, and LATS2 were more frequent in nonepithelioid MPM and positively associated with the S.score. BAP1, NF2, TERT promoter, TP53, and SETD2 mutations were enriched in some molecular subtypes. NF2 mutation rate was higher in asbestos unexposed patient. TERT promoter, NF2, and TP53 mutations were associated with a poorer overall survival. Our findings lead to a better characterization of MPM heterogeneity by identifying new significant associations between mutational status and histologic and molecular heterogeneity. Strikingly, we highlight the strong association between new mutations and overall survival. Our comprehensive genetic characterization of key‐altered genes including TERT promoter in malignant pleural mesothelioma led to the identification of new significant associations between the mutational status and the histological and molecular classifications. Our findings allow a better understanding of the genetic landscape in the context of tumor heterogeneity and highlight the high prognostic value of gene mutations in mesothelioma. |
| اللغة: | English |
| تدمد: | 1878-0261 1574-7891 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::abcd87b92bfdf2f6d6edeb61e7334dcaTest http://europepmc.org/articles/PMC7266286Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....abcd87b92bfdf2f6d6edeb61e7334dca |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18780261 15747891 |
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