{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:24:03Z","timestamp":1792009443338,"version":"4.4.0"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,13]],"date-time":"2020-06-13T00:00:00Z","timestamp":1592006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial proliferation that is most commonly encountered as an incidental finding in the peritoneal cavity. There is controversy in the literature about whether WDPM is a neoplasm or a reactive process and, if neoplastic, whether it is a variant or precursor of epithelial malignant mesothelioma or is a different entity. Using whole exome sequencing of five WDPMs of the peritoneum, we have identified distinct mutations in EHD1, ATM, FBXO10, SH2D2A, CDH5, MAGED1, and TP73 shared by WDPM cases but not reported in malignant mesotheliomas. Furthermore, we show that WDPM is strongly enriched with C &gt; A transversion substitution mutations, a pattern that is also not found in malignant mesotheliomas. The WDPMs lacked the alterations involving BAP1, SETD2, NF2, CDKN2A\/B, LASTS1\/2, PBRM1, and SMARCC1 that are frequently found in malignant mesotheliomas. We conclude that WDPMs are neoplasms that are genetically distinct from malignant mesotheliomas and, based on observed mutations, do not appear to be precursors of malignant mesotheliomas.<\/jats:p>","DOI":"10.3390\/cancers12061568","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T12:16:57Z","timestamp":1592223417000},"page":"1568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Well-Differentiated Papillary Mesothelioma of the Peritoneum Is Genetically Distinct from Malignant Mesothelioma"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1144-1413","authenticated-orcid":false,"given":"Raunak","family":"Shrestha","sequence":"first","affiliation":[{"name":"Vancouver Prostate Centre, Vancouver, BC V6H 3ZH, Canada"},{"name":"Department of Urologic Sciences, University of British Columbia, Vancouver, BC V5Z 1M9, Canada"},{"name":"Department of Radiation Oncology, University of California San Francisco, San Francisco, CA94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5471-6229","authenticated-orcid":false,"given":"Noushin","family":"Nabavi","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Vancouver, BC V6H 3ZH, Canada"},{"name":"Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav","family":"Volik","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Vancouver, BC V6H 3ZH, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"Anderson","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Vancouver, BC V6H 3ZH, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Haegert","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Vancouver, BC V6H 3ZH, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"McConeghy","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Vancouver, BC V6H 3ZH, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Funda","family":"Sar","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Vancouver, BC V6H 3ZH, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonal","family":"Brahmbhatt","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Vancouver, BC V6H 3ZH, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Bell","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Vancouver, BC V6H 3ZH, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Le Bihan","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Vancouver, BC V6H 3ZH, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9749-8591","authenticated-orcid":false,"given":"Yuzhuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Vancouver, BC V6H 3ZH, Canada"},{"name":"Department of Urologic Sciences, University of British Columbia, Vancouver, BC V5Z 1M9, Canada"},{"name":"Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Collins","sequence":"additional","affiliation":[{"name":"Vancouver Prostate Centre, Vancouver, BC V6H 3ZH, Canada"},{"name":"Department of Urologic Sciences, University of British Columbia, Vancouver, BC V5Z 1M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Churg","sequence":"additional","affiliation":[{"name":"Department of Pathology, Vancouver General Hospital, Vancouver, BC V5Z 1M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/1097-0142(19900115)65:2<292::AID-CNCR2820650218>3.0.CO;2-W","article-title":"Well-differentiated papillary mesothelioma of the peritoneum. A clinicopathologic study of 22 cases","volume":"65","author":"Daya","year":"1990","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1097\/00000478-200110000-00012","article-title":"Well-differentiated papillary mesothelioma","volume":"25","author":"Butnor","year":"2001","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.ejso.2018.10.065","article-title":"Well differentiated papillary peritoneal mesothelioma treated by cytoreduction and hyperthermic intraperitoneal chemotherapy-the experience of the PSOGI registry","volume":"45","author":"Deraco","year":"2019","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/ng.3520","article-title":"Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations","volume":"48","author":"Bueno","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1158\/2159-8290.CD-18-0804","article-title":"Integrative Molecular Characterization of Malignant Pleural Mesothelioma","volume":"8","author":"Hmeljak","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13073-019-0620-3","article-title":"BAP1 haploinsufficiency predicts a distinct immunogenic class of malignant peritoneal mesothelioma","volume":"11","author":"Shrestha","year":"2019","journal-title":"Genome Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"R96","DOI":"10.1186\/gb-2011-12-9-r96","article-title":"First somatic mutation of E2F1 in a critical DNA binding residue discovered in well-differentiated papillary mesothelioma of the peritoneum","volume":"12","author":"Yu","year":"2011","journal-title":"Genome Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.cancergen.2012.08.005","article-title":"Heterozygous loss of NF2 is an early molecular alteration in well-differentiated papillary mesothelioma of the peritoneum","volume":"205","author":"Nemoto","year":"2012","journal-title":"Cancer Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1093\/annonc\/mdt135","article-title":"Well-differentiated papillary mesothelioma: Clustering in a Portuguese family with a germline BAP1 mutation","volume":"24","author":"Ribeiro","year":"2013","journal-title":"Ann. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.humpath.2018.05.001","article-title":"BAP1 loss is unusual in well-differentiated papillary mesothelioma and may predict development of malignant mesothelioma","volume":"79","author":"Lee","year":"2018","journal-title":"Hum. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41379-018-0127-2","article-title":"Well-differentiated papillary mesothelioma of the peritoneum is genetically defined by mutually exclusive mutations in TRAF7 and CDC42","volume":"32","author":"Stevers","year":"2019","journal-title":"Mod. Pathol."},{"key":"ref_12","unstructured":"Travis, W.D., Brambilla, E., M\u00fcller-Hermelink, H.K., and Harris, C.C. (2004). Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart, WHO Press."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13059-016-0893-4","article-title":"DeconstructSigs: Delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution","volume":"17","author":"Rosenthal","year":"2016","journal-title":"Genome Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1038\/ng.3441","article-title":"Clock-like mutational processes in human somatic cells","volume":"47","author":"Alexandrov","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"D590","DOI":"10.1093\/nar\/gky962","article-title":"New approach for understanding genome variations in KEGG","volume":"47","author":"Kanehisa","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_16","unstructured":"(2017). AACR Project GENIE Consortium AACR Project GENIE: Powering Precision Medicine through an International Consortium. Cancer Discov., 7, 818\u2013831."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1177\/1947601911408890","article-title":"p73 in Cancer","volume":"2","author":"Rufini","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3109\/07853890.2011.573806","article-title":"MAGED1: Molecular insights and clinical implications","volume":"43","author":"Wang","year":"2011","journal-title":"Ann. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.cancergen.2015.12.006","article-title":"The risk for developing cancer in Israeli ATM, BLM, and FANCC heterozygous mutation carriers","volume":"209","author":"Laitman","year":"2016","journal-title":"Cancer Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1101\/gr.220038.116","article-title":"Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors","volume":"27","author":"Huang","year":"2017","journal-title":"Genome Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/ng.855","article-title":"The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma","volume":"43","author":"Bott","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.humpath.2016.04.015","article-title":"Genomic copy number alterations in 33 malignant peritoneal mesothelioma analyzed by comparative genomic hybridization array","volume":"55","author":"Chirac","year":"2016","journal-title":"Hum. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrc3647","article-title":"Beyond E-cadherin: Roles of other cadherin superfamily members in cancer","volume":"14","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nrm2755","article-title":"Pathways and mechanisms of endocytic recycling","volume":"10","author":"Grant","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/s41419-018-0447-7","article-title":"NF-\u03baB-driven improvement of EHD1 contributes to erlotinib resistance in EGFR-mutant lung cancers","volume":"9","author":"Wang","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3943","DOI":"10.1073\/pnas.1217271110","article-title":"Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma","volume":"110","author":"Chiorazzi","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/nri2397","article-title":"Tailoring T-cell receptor signals by proximal negative feedback mechanisms","volume":"8","author":"Acuto","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13432","DOI":"10.1073\/pnas.1612074113","article-title":"High-density array-CGH with targeted NGS unmask multiple noncontiguous minute deletions on chromosome 3p21 in mesothelioma","volume":"113","author":"Yoshikawa","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/modpathol.2017.153","article-title":"Adenomatoid tumors of the male and female genital tract are defined by TRAF7 mutations that drive aberrant NF-kB pathway activation","volume":"31","author":"Goode","year":"2018","journal-title":"Mod. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.lungcan.2018.03.009","article-title":"(Bill.; Patch, A.M.; Pearson, J.V.; Waddell, N.; Allcock, R.J.N.; Holt, R.A.; Robinson, B.W.S.; et al. Malignant cells from pleural fluids in malignant mesothelioma patients reveal novel mutations","volume":"119","author":"Sneddon","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/bib\/bbs017","article-title":"Integrative Genomics Viewer (IGV): High-performance genomics data visualization and exploration","volume":"14","author":"Robinson","year":"2013","journal-title":"Brief. Bioinform."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1101\/gr.239244.118","article-title":"Maftools: Efficient and comprehensive analysis of somatic variants in cancer","volume":"28","author":"Mayakonda","year":"2018","journal-title":"Genome Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"R41","DOI":"10.1186\/gb-2011-12-4-r41","article-title":"GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers","volume":"12","author":"Mermel","year":"2011","journal-title":"Genome Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/6\/1568\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:38:39Z","timestamp":1760175519000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/6\/1568"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,13]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["cancers12061568"],"URL":"https:\/\/doi.org\/10.3390\/cancers12061568","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/632810","asserted-by":"object"}]},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,13]]}}}