{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:09:23Z","timestamp":1772118563383,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,7,8]],"date-time":"2023-07-08T00:00:00Z","timestamp":1688774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000351","name":"British Lung Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000351","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Malignant pleural mesothelioma (MPM), a rare cancer a long latency period (up to 40\u2009years) between asbestos exposure and disease presentation. The mechanisms coupling asbestos to recurrent somatic alterations are poorly defined. Gene fusions arising through genomic instability may create novel drivers during early MPM evolution. We explored the gene fusions that occurred early in the evolutionary history of the tumor. We conducted multiregional whole exome sequencing (WES) of 106 samples from 20 patients undergoing pleurectomy decortication and identified 24 clonal nonrecurrent gene fusions, three of which were novel (\n                    <jats:italic>FMO9P\u2010OR2W5<\/jats:italic>\n                    ,\n                    <jats:italic>GBA3<\/jats:italic>\n                    , and\n                    <jats:italic>SP9<\/jats:italic>\n                    ). The number of early gene fusion events detected varied from zero to eight per tumor, and presence of gene fusions was associated with clonal losses involving the Hippo pathway genes and homologous recombination DNA repair genes. Fusions involved known tumor suppressors\n                    <jats:italic>BAP1<\/jats:italic>\n                    ,\n                    <jats:italic>MTAP<\/jats:italic>\n                    , and\n                    <jats:italic>LRP1B<\/jats:italic>\n                    , and a clonal oncogenic fusion involving\n                    <jats:italic>CACNA1D\u2010ERC2<\/jats:italic>\n                    ,\n                    <jats:italic>PARD3B<\/jats:italic>\n                    \u2010\n                    <jats:italic>NT5DC2<\/jats:italic>\n                    , and\n                    <jats:italic>STAB2<\/jats:italic>\n                    \u2010\n                    <jats:italic>NT5DC2<\/jats:italic>\n                    fusions were also identified as clonal fusions. Gene fusions events occur early during MPM evolution. Individual fusions are rare as no recurrent truncal fusions event were found. This suggests the importance of early disruption of these pathways in generating genomic rearrangements resulting in potentially oncogenic gene fusions.\n                  <\/jats:p>","DOI":"10.1002\/gcc.23189","type":"journal-article","created":{"date-parts":[[2023,7,8]],"date-time":"2023-07-08T06:36:22Z","timestamp":1688798182000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Gene fusions during the early evolution of mesothelioma correlate with impaired\n                    <scp>DNA<\/scp>\n                    repair and Hippo pathways"],"prefix":"10.1002","volume":"63","author":[{"given":"Maymun","family":"Jama","sequence":"first","affiliation":[{"name":"Department of Genetics and Genome Biology University of Leicester  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Mesothelioma Research Programme, Leicester Cancer Research Centre University of Leicester  Leicester UK"},{"name":"Novogene Corpotation Ltd., Building 301  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Poile","sequence":"additional","affiliation":[{"name":"Mesothelioma Research Programme, Leicester Cancer Research Centre University of Leicester  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Apostolos","family":"Nakas","sequence":"additional","affiliation":[{"name":"Thoracic Medical Oncology University Hospitals of Leicester NHS Trust  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annabel","family":"Sharkey","sequence":"additional","affiliation":[{"name":"Department of Cardio\u2010Thoracic Surgery Sheffield Teaching Hospital NHS Trust  Sheffield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Dzialo","sequence":"additional","affiliation":[{"name":"Mesothelioma Research Programme, Leicester Cancer Research Centre University of Leicester  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Dawson","sequence":"additional","affiliation":[{"name":"Thoracic Medical Oncology University Hospitals of Leicester NHS Trust  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kudazyi","family":"Kutywayo","sequence":"additional","affiliation":[{"name":"Mesothelioma Research Programme, Leicester Cancer Research Centre University of Leicester  Leicester UK"},{"name":"Department of Cardio\u2010Thoracic Surgery Sheffield Teaching Hospital NHS Trust  Sheffield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dean A.","family":"Fennell","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Biology University of Leicester  Leicester UK"},{"name":"Mesothelioma Research Programme, Leicester Cancer Research Centre University of Leicester  Leicester 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