{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T22:53:53Z","timestamp":1771455233052,"version":"3.50.1"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA258784"],"award-info":[{"award-number":["R01 CA258784"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["NCI R35 CA263816"],"award-info":[{"award-number":["NCI R35 CA263816"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genome Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Diffuse pleural mesothelioma (DPM) is an aggressive malignancy that, despite recent treatment advances, has unacceptably poor outcomes. Therapeutic research in DPM is inhibited by a paucity of preclinical models that faithfully recapitulate the human disease.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We established 22 patient-derived xenografts (PDX) from 22 patients with DPM and performed multi-omic analyses to deconvolute the mutational landscapes, global expression profiles, and molecular subtypes of these PDX models and compared features to those of the matched primary patient tumors. Targeted next-generation sequencing (NGS; MSK-IMPACT), immunohistochemistry, and histologic subtyping were performed on all available samples. RNA sequencing was performed on all available PDX samples. Clinical outcomes and treatment history were annotated for all patients. Platinum-doublet progression-free survival (PFS) was determined from the start of chemotherapy until radiographic\/clinical progression and grouped into &lt; or \u2265 6 months.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>PDX models were established from both treatment na\u00efve and previously treated samples and were noted to closely resemble the histology, genomic landscape, and proteomic profiles of the parent tumor. After establishing the validity of the models, transcriptomic analyses demonstrated overexpression in WNT\/\u03b2-catenin, hedgehog, and TGF-\u03b2 signaling and a consistent suppression of immune-related signaling in PDXs derived from patients with worse clinical outcomes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These data demonstrate that DPM PDX models closely resemble the genotype and phenotype of parental tumors, and identify pathways altered in DPM for future exploration in preclinical studies.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13073-022-01129-4","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T18:14:50Z","timestamp":1668536090000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genomic and transcriptomic analysis of a diffuse pleural mesothelioma patient-derived xenograft library"],"prefix":"10.1186","volume":"14","author":[{"given":"Michael","family":"Offin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Sauter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sam E.","family":"Tischfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacklynn V.","family":"Egger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shweta","family":"Chavan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nisargbhai S.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parvathy","family":"Manoj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katia","family":"Ventura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viola","family":"Allaj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"de Stanchina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Travis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Ladanyi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Rimner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie W.","family":"Rusch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prasad S.","family":"Adusumilli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John T.","family":"Poirier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjorie G.","family":"Zauderer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles M.","family":"Rudin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4673-7481","authenticated-orcid":false,"given":"Triparna","family":"Sen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"key":"1129_CR1","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1200\/JCO.2008.19.8523","volume":"27","author":"AS Tsao","year":"2009","unstructured":"Tsao AS, Wistuba I, Roth JA, Kindler HL. Malignant pleural mesothelioma. J Clin Oncol. 2009;27:2081\u201390. https:\/\/doi.org\/10.1200\/JCO.2008.19.8523.","journal-title":"J Clin Oncol"},{"key":"1129_CR2","unstructured":"Noone A, Howlander N, Krapcho M, et al. SEER Cancer Statistics Vol. based on November 2017 (SEER, 2017). https:\/\/seer.cancer.gov\/archive\/csr\/1975_2017\/."},{"key":"1129_CR3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.jtho.2019.08.2506","volume":"15","author":"AG Nicholson","year":"2020","unstructured":"Nicholson AG, et al. EURACAN\/IASLC proposals for updating the histologic classification of pleural mesothelioma: towards a more multidisciplinary approach. J Thorac Oncol. 2020;15:29\u201349. https:\/\/doi.org\/10.1016\/j.jtho.2019.08.2506.","journal-title":"J Thorac Oncol"},{"key":"1129_CR4","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1016\/j.jtho.2018.08.2036","volume":"13","author":"AS Tsao","year":"2018","unstructured":"Tsao AS, et al. Current and future management of malignant mesothelioma: a consensus report from the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation. J Thorac Oncol. 2018;13:1655\u201367. https:\/\/doi.org\/10.1016\/j.jtho.2018.08.2036.","journal-title":"J Thorac Oncol"},{"key":"1129_CR5","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.1200\/jco.2016.67.2675","volume":"34","author":"A Rimner","year":"2016","unstructured":"Rimner A, et al. Phase II study of hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) as part of lung-sparing multimodality therapy in patients with malignant pleural mesothelioma. J Clin Oncol. 2016;34:2761\u20138. https:\/\/doi.org\/10.1200\/jco.2016.67.2675.","journal-title":"J Clin Oncol"},{"key":"1129_CR6","doi-asserted-by":"publisher","first-page":"502","DOI":"10.3978\/j.issn.2225-319X.2012.11.12","volume":"1","author":"W Weder","year":"2012","unstructured":"Weder W, Opitz I. Multimodality therapy for malignant pleural mesothelioma. Ann Cardiothorac Surg. 2012;1:502\u20137. https:\/\/doi.org\/10.3978\/j.issn.2225-319X.2012.11.12.","journal-title":"Ann Cardiothorac Surg"},{"key":"1129_CR7","doi-asserted-by":"publisher","first-page":"2636","DOI":"10.1200\/JCO.2003.11.136","volume":"21","author":"NJ Vogelzang","year":"2003","unstructured":"Vogelzang NJ, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21:2636\u201344. https:\/\/doi.org\/10.1200\/JCO.2003.11.136.","journal-title":"J Clin Oncol"},{"key":"1129_CR8","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/s0140-6736(20)32714-8","volume":"397","author":"P Baas","year":"2021","unstructured":"Baas P, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021;397:375\u201386. https:\/\/doi.org\/10.1016\/s0140-6736(20)32714-8.","journal-title":"Lancet"},{"key":"1129_CR9","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1200\/JCO.1998.16.1.145","volume":"16","author":"D Curran","year":"1998","unstructured":"Curran D, et al. Prognostic factors in patients with pleural mesothelioma: the European Organization for Research and Treatment of Cancer experience. J Clin Oncol. 1998;16:145\u201352. https:\/\/doi.org\/10.1200\/JCO.1998.16.1.145.","journal-title":"J Clin Oncol"},{"key":"1129_CR10","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/bjc.2012.245","volume":"107","author":"S van der Bij","year":"2012","unstructured":"van der Bij S, et al. Prognosis and prognostic factors of patients with mesothelioma: a population-based study. Br J Cancer. 2012;107:161\u20134. https:\/\/doi.org\/10.1038\/bjc.2012.245.","journal-title":"Br J Cancer"},{"key":"1129_CR11","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1002\/ijc.23874","volume":"124","author":"F Montanaro","year":"2009","unstructured":"Montanaro F, et al. Survival of pleural malignant mesothelioma in Italy: a population-based study. Int J Cancer. 2009;124:201\u20137. https:\/\/doi.org\/10.1002\/ijc.23874.","journal-title":"Int J Cancer"},{"key":"1129_CR12","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.1016\/j.jtho.2018.08.007","volume":"13","author":"Y Metaxas","year":"2018","unstructured":"Metaxas Y, et al. Pembrolizumab as palliative immunotherapy in malignant pleural mesothelioma. J Thorac Oncol. 2018;13:1784\u201391. https:\/\/doi.org\/10.1016\/j.jtho.2018.08.007.","journal-title":"J Thorac Oncol"},{"key":"1129_CR13","doi-asserted-by":"publisher","first-page":"9003","DOI":"10.1200\/JCO.2020.38.15_suppl.9003","volume":"38","author":"PM Forde","year":"2020","unstructured":"Forde PM, et al. PrE0505: Phase II multicenter study of anti-PD-L1, durvalumab, in combination with cisplatin and pemetrexed for the first-line treatment of unresectable malignant pleural mesothelioma (MPM)\u2014A PrECOG LLC study. J Clin Oncol. 2020;38:9003. https:\/\/doi.org\/10.1200\/JCO.2020.38.15_suppl.9003.","journal-title":"J Clin Oncol"},{"key":"1129_CR14","doi-asserted-by":"publisher","first-page":"388","DOI":"10.3389\/fonc.2020.00388","volume":"10","author":"C Blanquart","year":"2020","unstructured":"Blanquart C, Jaurand M-C, Jean D. The biology of malignant mesothelioma and the relevance of preclinical models. Front Oncol. 2020;10:388. https:\/\/doi.org\/10.3389\/fonc.2020.00388.","journal-title":"Front Oncol"},{"key":"1129_CR15","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1136\/thoraxjnl-2015-207496","volume":"71","author":"RC Rintoul","year":"2016","unstructured":"Rintoul RC, Rassl DM, Gittins J, Marciniak SJ. MesobanK UK: an international mesothelioma bioresource. Thorax. 2016;71:380\u20132. https:\/\/doi.org\/10.1136\/thoraxjnl-2015-207496.","journal-title":"Thorax"},{"key":"1129_CR16","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13039-020-00511-4","volume":"13","author":"E Wahlbuhl","year":"2020","unstructured":"Wahlbuhl E, Liehr T, Rincic M, Azawi S. Cytogenomic characterization of three murine malignant mesothelioma tumor cell lines. Mol Cytogenet. 2020;13:43. https:\/\/doi.org\/10.1186\/s13039-020-00511-4.","journal-title":"Mol Cytogenet"},{"key":"1129_CR17","doi-asserted-by":"publisher","unstructured":"Johnson BW, Takahashi K, Cheng YY. Preclinical models and resources to facilitate basic science research on malignant mesothelioma \u2013 a review. Front Oncol. 2021;11. https:\/\/doi.org\/10.3389\/fonc.2021.748444.","DOI":"10.3389\/fonc.2021.748444"},{"key":"1129_CR18","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1186\/s12885-015-1362-2","volume":"15","author":"N Kalra","year":"2015","unstructured":"Kalra N, et al. Mesothelioma patient derived tumor xenografts with defined BAP1 mutations that mimic the molecular characteristics of human malignant mesothelioma. BMC Cancer. 2015;15:376. https:\/\/doi.org\/10.1186\/s12885-015-1362-2.","journal-title":"BMC Cancer"},{"key":"1129_CR19","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.3390\/ijms19082191","volume":"19","author":"D Jean","year":"2018","unstructured":"Jean D, Jaurand M-C. Mesotheliomas in genetically engineered mice unravel mechanism of mesothelial carcinogenesis. Int J Mol Sci. 2018;19:2191.","journal-title":"Int J Mol Sci"},{"key":"1129_CR20","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1186\/s12885-017-3382-6","volume":"17","author":"S Sneddon","year":"2017","unstructured":"Sneddon S, et al. Whole exome sequencing of an asbestos-induced wild-type murine model of malignant mesothelioma. BMC Cancer. 2017;17:396. https:\/\/doi.org\/10.1186\/s12885-017-3382-6.","journal-title":"BMC Cancer"},{"key":"1129_CR21","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1158\/1078-0432.Ccr-16-0844","volume":"23","author":"L Wu","year":"2017","unstructured":"Wu L, et al. Patient-derived xenograft establishment from human malignant pleural mesothelioma. Clin Cancer Res. 2017;23:1060\u20137. https:\/\/doi.org\/10.1158\/1078-0432.Ccr-16-0844.","journal-title":"Clin Cancer Res"},{"key":"1129_CR22","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1186\/1756-0500-5-482","volume":"5","author":"A Bearz","year":"2012","unstructured":"Bearz A, et al. Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience. BMC Res Notes. 2012;5:482. https:\/\/doi.org\/10.1186\/1756-0500-5-482.","journal-title":"BMC Res Notes"},{"key":"1129_CR23","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.lungcan.2010.12.004","volume":"72","author":"GL Ceresoli","year":"2011","unstructured":"Ceresoli GL, et al. Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma. Lung Cancer. 2011;72:73\u20137. https:\/\/doi.org\/10.1016\/j.lungcan.2010.12.004.","journal-title":"Lung Cancer"},{"key":"1129_CR24","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.lungcan.2011.08.011","volume":"75","author":"PA Zucali","year":"2012","unstructured":"Zucali PA, et al. Second-line chemotherapy in malignant pleural mesothelioma: results of a retrospective multicenter survey. Lung Cancer. 2012;75:360\u20137. https:\/\/doi.org\/10.1016\/j.lungcan.2011.08.011.","journal-title":"Lung Cancer"},{"key":"1129_CR25","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.1038\/s41591-021-01541-0","volume":"27","author":"PM Forde","year":"2021","unstructured":"Forde PM, et al. Durvalumab with platinum-pemetrexed for unresectable pleural mesothelioma: survival, genomic and immunologic analyses from the phase 2 PrE0505 trial. Nat Med. 2021;27:1910\u201320. https:\/\/doi.org\/10.1038\/s41591-021-01541-0.","journal-title":"Nat Med"},{"key":"1129_CR26","doi-asserted-by":"publisher","first-page":"3364","DOI":"10.1158\/0008-5472.Can-08-4210","volume":"69","author":"VC Daniel","year":"2009","unstructured":"Daniel VC, et al. A primary xenograft model of small-cell lung cancer reveals irreversible changes in gene expression imposed by culture in vitro. Cancer Res. 2009;69:3364\u201373. https:\/\/doi.org\/10.1158\/0008-5472.Can-08-4210.","journal-title":"Cancer Res"},{"key":"1129_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108444","volume":"33","author":"CA Wohlhieter","year":"2020","unstructured":"Wohlhieter CA, et al. Concurrent mutations in STK11 and KEAP1 promote ferroptosis protection and SCD1 dependence in lung cancer. Cell Rep. 2020;33:108444. https:\/\/doi.org\/10.1016\/j.celrep.2020.108444.","journal-title":"Cell Rep"},{"key":"1129_CR28","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15\u201321. https:\/\/doi.org\/10.1093\/bioinformatics\/bts635.","journal-title":"Bioinformatics"},{"key":"1129_CR29","unstructured":"WHO Classification of Tumours: Thoracic Tumours. 5th ed, Vol. 5. World Health Organization;\u00a02021. https:\/\/publications.iarc.fr\/Book-And-Report-Series\/Who-Classification-Of-Tumours\/Thoracic-Tumours-2021."},{"key":"1129_CR30","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/modpathol.2011.146","volume":"25","author":"K Kadota","year":"2012","unstructured":"Kadota K, et al. A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma. Mod Pathol. 2012;25:260\u201371. https:\/\/doi.org\/10.1038\/modpathol.2011.146.","journal-title":"Mod Pathol"},{"key":"1129_CR31","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.jmoldx.2014.12.006","volume":"17","author":"DT Cheng","year":"2015","unstructured":"Cheng DT, et al. Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT): a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology. J Mol Diagn. 2015;17:251\u201364. https:\/\/doi.org\/10.1016\/j.jmoldx.2014.12.006.","journal-title":"J Mol Diagn"},{"key":"1129_CR32","doi-asserted-by":"publisher","unstructured":"Zauderer MG, et al. The use of a next-generation sequencing-derived machine-learning risk-prediction model (OncoCast-MPM) for malignant pleural mesothelioma: a retrospective study. Lancet Digit Health. 2021. https:\/\/doi.org\/10.1016\/s2589-7500(21)00104-7.","DOI":"10.1016\/s2589-7500(21)00104-7"},{"key":"1129_CR33","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw520","volume":"44","author":"R Shen","year":"2016","unstructured":"Shen R, Seshan VE. FACETS: allele-specific copy number and clonal heterogeneity analysis tool for high-throughput DNA sequencing. Nucleic Acids Res. 2016;44:e131. https:\/\/doi.org\/10.1093\/nar\/gkw520.","journal-title":"Nucleic Acids Res"},{"key":"1129_CR34","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1158\/2159-8290.Cd-18-0804","volume":"8","author":"J Hmeljak","year":"2018","unstructured":"Hmeljak J, et al. Integrative molecular characterization of malignant pleural mesothelioma. Cancer Discov. 2018;8:1548\u201365. https:\/\/doi.org\/10.1158\/2159-8290.Cd-18-0804.","journal-title":"Cancer Discov"},{"key":"1129_CR35","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/modpathol.2017.170","volume":"31","author":"LE Rosen","year":"2018","unstructured":"Rosen LE, et al. Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study. Mod Pathol. 2018;31:598\u2013606. https:\/\/doi.org\/10.1038\/modpathol.2017.170.","journal-title":"Mod Pathol"},{"key":"1129_CR36","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s13000-021-01125-z","volume":"16","author":"F Pezzuto","year":"2021","unstructured":"Pezzuto F, et al. Evaluation of prognostic histological parameters proposed for pleural mesothelioma in diffuse malignant peritoneal mesothelioma. A short report. Diagn Pathol. 2021;16:64. https:\/\/doi.org\/10.1186\/s13000-021-01125-z.","journal-title":"Diagn Pathol"},{"key":"1129_CR37","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1097\/JTO.0b013e318211127a","volume":"6","author":"K Kadota","year":"2011","unstructured":"Kadota K, et al. Pleomorphic epithelioid diffuse malignant pleural mesothelioma: a clinicopathological review and conceptual proposal to reclassify as biphasic or sarcomatoid mesothelioma. J Thorac Oncol. 2011;6:896\u2013904. https:\/\/doi.org\/10.1097\/JTO.0b013e318211127a.","journal-title":"J Thorac Oncol"},{"key":"1129_CR38","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/ng.855","volume":"43","author":"M Bott","year":"2011","unstructured":"Bott M, et al. The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nat Genet. 2011;43:668\u201372. https:\/\/doi.org\/10.1038\/ng.855.","journal-title":"Nat Genet"},{"key":"1129_CR39","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s13073-019-0620-3","volume":"11","author":"R Shrestha","year":"2019","unstructured":"Shrestha R, et al. BAP1 haploinsufficiency predicts a distinct immunogenic class of malignant peritoneal mesothelioma. Genome Med. 2019;11:8. https:\/\/doi.org\/10.1186\/s13073-019-0620-3.","journal-title":"Genome Med"},{"key":"1129_CR40","first-page":"344","volume":"146","author":"KM Amin","year":"1995","unstructured":"Amin KM, et al. Wilms\u2019 tumor 1 susceptibility (WT1) gene products are selectively expressed in malignant mesothelioma. Am J Pathol. 1995;146:344\u201356.","journal-title":"Am J Pathol"},{"key":"1129_CR41","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1007\/s12094-013-1146-6","volume":"16","author":"S Cedr\u00e9s","year":"2014","unstructured":"Cedr\u00e9s S, et al. Expression of Wilms\u2019 tumor gene (WT1) is associated with survival in malignant pleural mesothelioma. Clin Transl Oncol. 2014;16:776\u201382. https:\/\/doi.org\/10.1007\/s12094-013-1146-6.","journal-title":"Clin Transl Oncol"},{"key":"1129_CR42","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1007\/s12253-016-0181-3","volume":"23","author":"T Pl\u00f6nes","year":"2017","unstructured":"Pl\u00f6nes T, et al. Turning back the Wheel: Inducing mesenchymal to epithelial transition via Wilms tumor 1 knockdown in human mesothelioma cell lines to influence proliferation, invasiveness, and chemotaxis. Pathol Oncol Res. 2017;23:723\u201330. https:\/\/doi.org\/10.1007\/s12253-016-0181-3.","journal-title":"Pathol Oncol Res"},{"key":"1129_CR43","doi-asserted-by":"publisher","first-page":"397","DOI":"10.3390\/biomedicines9040397","volume":"9","author":"S Weidemann","year":"2021","unstructured":"Weidemann S, et al. Mesothelin expression in human tumors: a tissue microarray study on 12,679 tumors. Biomedicines. 2021;9:397. https:\/\/doi.org\/10.3390\/biomedicines9040397.","journal-title":"Biomedicines"},{"key":"1129_CR44","doi-asserted-by":"publisher","first-page":"26744","DOI":"10.18632\/oncotarget.15814","volume":"8","author":"S Inaguma","year":"2017","unstructured":"Inaguma S, et al. Comprehensive immunohistochemical study of mesothelin (MSLN) using different monoclonal antibodies 5B2 and MN-1 in 1562 tumors with evaluation of its prognostic value in malignant pleural mesothelioma. Oncotarget. 2017;8:26744\u201354. https:\/\/doi.org\/10.18632\/oncotarget.15814.","journal-title":"Oncotarget"},{"key":"1129_CR45","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1016\/S1470-2045(20)30462-9","volume":"21","author":"AK Nowak","year":"2020","unstructured":"Nowak AK, et al. Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in. Lancet Oncol. 2020;21:1213\u201323. https:\/\/doi.org\/10.1016\/S1470-2045(20)30462-9.","journal-title":"Lancet Oncol"},{"key":"1129_CR46","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1016\/j.jtho.2018.05.038","volume":"13","author":"J Quispel-Janssen","year":"2018","unstructured":"Quispel-Janssen J, et al. Programmed death 1 blockade with nivolumab in patients with recurrent malignant pleural mesothelioma. J Thorac Oncol. 2018;13:1569\u201376. https:\/\/doi.org\/10.1016\/j.jtho.2018.05.038.","journal-title":"J Thorac Oncol"},{"key":"1129_CR47","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/s1470-2045(17)30169-9","volume":"18","author":"EW Alley","year":"2017","unstructured":"Alley EW, et al. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2017;18:623\u201330. https:\/\/doi.org\/10.1016\/s1470-2045(17)30169-9.","journal-title":"Lancet Oncol"},{"key":"1129_CR48","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/s41379-019-0364-z","volume":"33","author":"S Muller","year":"2020","unstructured":"Muller S, et al. V-domain Ig-containing suppressor of T-cell activation (VISTA), a potentially targetable immune checkpoint molecule, is highly expressed in epithelioid malignant pleural mesothelioma. Mod Pathol. 2020;33:303\u201311. https:\/\/doi.org\/10.1038\/s41379-019-0364-z.","journal-title":"Mod Pathol"},{"key":"1129_CR49","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/ng.3520","volume":"48","author":"R Bueno","year":"2016","unstructured":"Bueno R, et al. Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nat Genet. 2016;48:407\u201316. https:\/\/doi.org\/10.1038\/ng.3520.","journal-title":"Nat Genet"},{"key":"1129_CR50","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s13073-022-01060-8","volume":"14","author":"J Creaney","year":"2022","unstructured":"Creaney J, et al. Comprehensive genomic and tumour immune profiling reveals potential therapeutic targets in malignant pleural mesothelioma. Genome Med. 2022;14:58. https:\/\/doi.org\/10.1186\/s13073-022-01060-8.","journal-title":"Genome Med"},{"key":"1129_CR51","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1158\/2159-8290.CD-17-0226","volume":"7","author":"KW Mouw","year":"2017","unstructured":"Mouw KW, Goldberg MS, Konstantinopoulos PA, Andrea AD. DNA damage and repair biomarkers of immunotherapy response. Cancer Discov. 2017;7:675. https:\/\/doi.org\/10.1158\/2159-8290.CD-17-0226.","journal-title":"Cancer Discov"},{"key":"1129_CR52","doi-asserted-by":"publisher","first-page":"108080","DOI":"10.1016\/j.celrep.2020.108080","volume":"32","author":"J Chen","year":"2020","unstructured":"Chen J, et al. Cell cycle checkpoints cooperate to suppress DNA- and RNA-associated molecular pattern recognition and anti-tumor immune responses. Cell Rep. 2020;32:108080. https:\/\/doi.org\/10.1016\/j.celrep.2020.108080.","journal-title":"Cell Rep"},{"key":"1129_CR53","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1038\/s41416-021-01462-2","volume":"125","author":"J Obacz","year":"2021","unstructured":"Obacz J, et al. Biological basis for novel mesothelioma therapies. Br J Cancer. 2021;125:1039\u201355. https:\/\/doi.org\/10.1038\/s41416-021-01462-2.","journal-title":"Br J Cancer"},{"key":"1129_CR54","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/s1470-2045(22)00277-7","volume":"23","author":"MG Zauderer","year":"2022","unstructured":"Zauderer MG, et al. EZH2 inhibitor tazemetostat in patients with relapsed or refractory, BAP1-inactivated malignant pleural mesothelioma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2022;23:758\u201367. https:\/\/doi.org\/10.1016\/s1470-2045(22)00277-7.","journal-title":"Lancet Oncol"},{"key":"1129_CR55","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/S1470-2045(22)00062-6","volume":"23","author":"DA Fennell","year":"2022","unstructured":"Fennell DA, et al. Abemaciclib in patients with p16ink4A-deficient mesothelioma (MiST2): a single-arm, open-label, phase 2 trial. Lancet Oncol. 2022;23:374\u201381. https:\/\/doi.org\/10.1016\/S1470-2045(22)00062-6.","journal-title":"Lancet Oncol"},{"key":"1129_CR56","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtocrr.2021.100231","volume":"2","author":"A Ghafoor","year":"2021","unstructured":"Ghafoor A, et al. Phase 2 study of olaparib in malignant mesothelioma and correlation of efficacy with germline or somatic mutations in BAP1 gene. JTO Clin Res Rep. 2021;2:100231. https:\/\/doi.org\/10.1016\/j.jtocrr.2021.100231.","journal-title":"JTO Clin Res Rep"},{"key":"1129_CR57","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1158\/1535-7163.Mct-16-0821","volume":"16","author":"J Cooper","year":"2017","unstructured":"Cooper J, et al. Combined inhibition of NEDD8-activating enzyme and mTOR suppresses NF2 loss-driven tumorigenesis. Mol Cancer Ther. 2017;16:1693\u2013704. https:\/\/doi.org\/10.1158\/1535-7163.Mct-16-0821.","journal-title":"Mol Cancer Ther"},{"key":"1129_CR58","doi-asserted-by":"publisher","first-page":"4646","DOI":"10.1158\/1078-0432.Ccr-12-0599","volume":"18","author":"Y Shi","year":"2012","unstructured":"Shi Y, et al. Role of hedgehog signaling in malignant pleural mesothelioma. Clin Cancer Res. 2012;18:4646\u201356. https:\/\/doi.org\/10.1158\/1078-0432.Ccr-12-0599.","journal-title":"Clin Cancer Res"},{"key":"1129_CR59","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066685","volume":"8","author":"CB Lim","year":"2013","unstructured":"Lim CB, et al. Mutational analysis of hedgehog signaling pathway genes in human malignant mesothelioma. PLoS One. 2013;8:e66685. https:\/\/doi.org\/10.1371\/journal.pone.0066685.","journal-title":"PLoS One"},{"key":"1129_CR60","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1158\/1541-7786.Mcr-21-0837","volume":"20","author":"E Sementino","year":"2022","unstructured":"Sementino E, et al. Inactivation of p21-activated kinase 2 (Pak2) inhibits the development of Nf2-deficient tumors by restricting downstream hedgehog and Wnt signaling. Mol Cancer Res. 2022;20:699\u2013711. https:\/\/doi.org\/10.1158\/1541-7786.Mcr-21-0837.","journal-title":"Mol Cancer Res"},{"key":"1129_CR61","doi-asserted-by":"publisher","first-page":"9390878-9390878","DOI":"10.1155\/2020\/9390878","volume":"2020","author":"S Yuan","year":"2020","unstructured":"Yuan S, et al. Role of Wnt\/\u03b2-catenin signaling in the chemoresistance modulation of colorectal cancer. Biomed Res Int. 2020;2020:9390878-9390878. https:\/\/doi.org\/10.1155\/2020\/9390878.","journal-title":"Biomed Res Int"},{"key":"1129_CR62","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1038\/nature06835","volume":"452","author":"I Malanchi","year":"2008","unstructured":"Malanchi I, et al. Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling. Nature. 2008;452:650\u20133. https:\/\/doi.org\/10.1038\/nature06835.","journal-title":"Nature"},{"key":"1129_CR63","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1158\/0008-5472.CAN-14-1327","volume":"75","author":"M Ilmer","year":"2015","unstructured":"Ilmer M, et al. RSPO2 enhances canonical Wnt signaling to confer stemness-associated traits to susceptible pancreatic cancer cells. Cancer Res. 2015;75:1883. https:\/\/doi.org\/10.1158\/0008-5472.CAN-14-1327.","journal-title":"Cancer Res"},{"key":"1129_CR64","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1038\/onc.2016.304","volume":"36","author":"T Zhan","year":"2017","unstructured":"Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene. 2017;36:1461\u201373. https:\/\/doi.org\/10.1038\/onc.2016.304.","journal-title":"Oncogene"},{"key":"1129_CR65","doi-asserted-by":"publisher","first-page":"8640","DOI":"10.1038\/ncomms9640","volume":"6","author":"L Fang","year":"2015","unstructured":"Fang L, et al. Aberrantly expressed miR-582-3p maintains lung cancer stem cell-like traits by activating Wnt\/\u03b2-catenin signalling. Nat Commun. 2015;6:8640. https:\/\/doi.org\/10.1038\/ncomms9640.","journal-title":"Nat Commun"},{"key":"1129_CR66","unstructured":"RNAseq analysis of meso PDX models. E-MTAB-11783. Arrayexpress. Public in ArrayExpress; 2022. https:\/\/www.ebi.ac.uk\/biostudies\/arrayexpress\/studies\/E-MTAB-11783?accession=E-MTAB-11783."}],"container-title":["Genome Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-022-01129-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13073-022-01129-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-022-01129-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T18:18:05Z","timestamp":1668536285000},"score":1,"resource":{"primary":{"URL":"https:\/\/genomemedicine.biomedcentral.com\/articles\/10.1186\/s13073-022-01129-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,15]]},"references-count":66,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["1129"],"URL":"https:\/\/doi.org\/10.1186\/s13073-022-01129-4","relation":{},"ISSN":["1756-994X"],"issn-type":[{"value":"1756-994X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,15]]},"assertion":[{"value":"20 February 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 October 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 November 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All human tissue obtained for PDX generation was from patients with a diagnosis of DPM who gave informed consent on an IRB-approved protocol at Memorial Sloan Kettering Cancer Center (MSK; 06-107 and\/or 12-245). All animal experiments were approved by the Memorial Sloan Kettering Cancer Center (MSK; 14-091) Animal Care and Use Committee and mice were housed in accredited facilities under pathogen-free conditions. All study procedures were conducted in accordance with the US Common Rule which is an ethical standard established for conduct of any US government-funded research and conformed to the principles of the Helsinki Declaration.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MDO has consulted regarding oncology drug development with Novartis, Jazz, and PharmaMar. MDO has received honorarium from Targeted Oncology, OncLive, and the American Society for Radiation Oncology.AR has consulted regarding oncology drug development with AstraZeneca, Merck, Boehringer Ingelheim, and Cybrexa. AR has received honorarium from MoreHealth and ResearchToPractice. AR serves on the scientific advisory boards of Merck. AR has received grants from Varian Medical Systems, Boehringer Ingelheim, Pfizer, AstraZeneca, and Merck.PSA has intellectual property and licensing royalties on mesothelin-targeted CAR T cell therapy, serves on scientific boards of Atara Bio, Bayer, BioArdis, Carisma therapeutics, Immugene, ImmPACT bio; consulted for Atara, Bayer; and has received research support from Atara BioMGZ has received consulting fees from Ikena, Takeda, GlaxoSmithKline, Aldeyra Therapeutics, and Novocure and honoraria for CME content from PER, Medscape, Research to Practice, Medical Learning Institute and OncLive. Memorial Sloan Kettering receives research funding from the Department of Defense, the National Institutes of Health, Precog, GlaxoSmithKline, Epizyme, Polaris, Sellas Life Sciences, Bristol Myers Squibb, Millenium\/Takeda, Curis, and Atara for research conducted by MGZ. MGZ serves as Chair of the Board of Directors of the Mesothelioma Applied Research Foundation, an uncompensated position.CMR has consulted regarding oncology drug development with Amgen, Daiichi Sankyo, Genentech\/Roche, Ipsen, Jazz, Merck, Pfizer, Syros, and Vavotek. CMR serves on the scientific advisory boards of Bridge Medicines, Earli, and Harpoon Therapeutics.TS has research funding from Jazz Pharmaceuticals.The remaining authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"127"}}