{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:09Z","timestamp":1788998409679,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,12,25]],"date-time":"2022-12-25T00:00:00Z","timestamp":1671926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Clear cell mesothelioma is uncommon and shows predominance of clear cells with resemblance to clear cell carcinomas. Clinicopathologic and molecular descriptions of clear cell mesothelioma remained limited. In this study, we identified an index patient with clear cell mesothelioma, confirmed by immunohistochemical and ultrastructural studies. Targeted next\u2010generation sequencing revealed the presence of an inactivating <jats:italic>VHL<\/jats:italic> mutation. We then systematically searched for <jats:italic>VHL<\/jats:italic>\u2010mutant mesotheliomas in a comprehensive genomic profiling database of 1532 mesotheliomas. Collectively, we identified a cohort of four <jats:italic>VHL<\/jats:italic>\u2010mutant clear cell mesotheliomas, including three peritoneal and one pleural tumors from three females and one male, with age range of 47\u201368 (median 63) years. Histologically, each tumor showed a microcystic to tubulopapillary architecture with prominent clear cells. By next\u2010generation DNA sequencing, each of the four clear cell mesotheliomas harbored inactivating <jats:italic>VHL<\/jats:italic> mutations, while lacking other alterations typical of mesotheliomas such as <jats:italic>BAP1<\/jats:italic>, <jats:italic>NF2<\/jats:italic>, <jats:italic>SETD2<\/jats:italic>, <jats:italic>CDKN2A<\/jats:italic>, <jats:italic>CDKN2B<\/jats:italic>, <jats:italic>TP53<\/jats:italic>, and <jats:italic>PTEN<\/jats:italic>. By using low\u2010pass whole genome sequencing on the index case and targeted next\u2010generation sequencing on the remaining three cases, we identified extensive loss of heterozygosity throughout the genome but consistently sparing chromosomes 5, 7, and 20, characteristic of genomic near\u2010haploidization. In summary, clear cell mesotheliomas were characterized by inactivating <jats:italic>VHL<\/jats:italic> mutations and genomic near\u2010haploidization and appeared to represent a distinct clinicopathologic and molecular category of mesotheliomas. Our findings implicate <jats:italic>VHL<\/jats:italic> in the pathogenesis of a subset of mesotheliomas, particularly those with clear cell morphology.<\/jats:p>","DOI":"10.1002\/gcc.23119","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T13:29:38Z","timestamp":1671024578000},"page":"267-274","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Clear cell mesotheliomas with inactivating <i>VHL<\/i> mutations and near\u2010haploid genomic features"],"prefix":"10.1002","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4403-7027","authenticated-orcid":false,"given":"Michael","family":"Michal","sequence":"first","affiliation":[{"name":"Department of Pathology Faculty of Medicine in Plzen, Charles University  Plzen Czech Republic"},{"name":"Department of Pathology Bioptical Laboratory Ltd.  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Cambridge Massachusetts USA"},{"name":"Department of Pathology and Laboratory Medicine Sylvester Comprehensive Cancer Center, and Jackson Memorial Hospitals, University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8568-1591","authenticated-orcid":false,"given":"Yin P.","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,25]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"204","volume-title":"WHO Classification of Tumours Thoracic Tumours","author":"Sauter 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