{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:58:51Z","timestamp":1792191531948,"version":"4.4.0"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T00:00:00Z","timestamp":1583798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004099","name":"Ligue Contre le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010466","name":"Chancellerie des Universit\u00e9s de Paris","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010466","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la Recherche sur le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:p>\n                    Development of precision medicine for malignant pleural mesothelioma (MPM) requires a deep knowledge of tumor heterogeneity. Histologic and molecular classifications and histo\u2010molecular 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\u2010generation sequencing was performed focusing on the major MPM mutated genes and the\n                    <jats:italic>TERT<\/jats:italic>\n                    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\u2010like and sarcomatoid\u2010like components (E\/S.scores). The mutation frequencies are consistent with literature data, but this study emphasized that\n                    <jats:italic>TERT<\/jats:italic>\n                    promoter, not considered by previous large sequencing studies, was the third locus most affected by mutations in MPM. Mutations in\n                    <jats:italic>TERT<\/jats:italic>\n                    promoter,\n                    <jats:italic>NF2,<\/jats:italic>\n                    and\n                    <jats:italic>LATS2<\/jats:italic>\n                    were more frequent in nonepithelioid MPM and positively associated with the S.score.\n                    <jats:italic>BAP1<\/jats:italic>\n                    ,\n                    <jats:italic>NF2<\/jats:italic>\n                    ,\n                    <jats:italic>TERT<\/jats:italic>\n                    promoter,\n                    <jats:italic>TP53,<\/jats:italic>\n                    and\n                    <jats:italic>SETD2<\/jats:italic>\n                    mutations were enriched in some molecular subtypes.\n                    <jats:italic>NF2<\/jats:italic>\n                    mutation rate was higher in asbestos unexposed patient.\n                    <jats:italic>TERT<\/jats:italic>\n                    promoter,\n                    <jats:italic>NF2,<\/jats:italic>\n                    and\n                    <jats:italic>TP53<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.12651","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T09:06:23Z","timestamp":1582275983000},"page":"1207-1223","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":105,"title":["Genetic alterations of malignant pleural mesothelioma: association\u00a0with tumor heterogeneity and overall survival"],"prefix":"10.1002","volume":"14","author":[{"given":"Lisa","family":"Quetel","sequence":"first","affiliation":[{"name":"Centre de Recherche des Cordeliers Inserm Sorbonne Universit\u00e9 Universit\u00e9 de Paris Functional Genomics of Solid Tumors laboratory France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9ment","family":"Meiller","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers Inserm 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