{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:09:16Z","timestamp":1760148556034,"version":"build-2065373602"},"reference-count":87,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004361","name":"Swiss Cancer League","doi-asserted-by":"publisher","award":["KLS-4538-08-2018","UZH STEB-22, -001","UFR20070801"],"award-info":[{"award-number":["KLS-4538-08-2018","UZH STEB-22, -001","UFR20070801"]}],"id":[{"id":"10.13039\/501100004361","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Stiftung f\u00fcr wissenschaftliche Forschung an der UZH\/Erbschaft B\u00fchler","award":["KLS-4538-08-2018","UZH STEB-22, -001","UFR20070801"],"award-info":[{"award-number":["KLS-4538-08-2018","UZH STEB-22, -001","UFR20070801"]}]},{"name":"SAKF (Stiftung f\u00fcr angewandte Krebsforschung)","award":["KLS-4538-08-2018","UZH STEB-22, -001","UFR20070801"],"award-info":[{"award-number":["KLS-4538-08-2018","UZH STEB-22, -001","UFR20070801"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cell lines are extensively used to study cancer biology. However, the use of highly passaged commercial cell lines has to be questioned, as they do not closely resemble the originating tumor. To understand the reliability of preclinical models for Malignant pleural mesothelioma (MPM) studies, we have performed whole transcriptome and whole exome analyses of fresh frozen MPM tumors and compared them to cell lines generated from these tumors, as well as commercial cell lines and a preclinical MPM mouse model. Patient-derived cell lines were generated from digested fresh tumors and whole exome sequencing was performed on DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor samples, corresponding patient-derived cell lines, and normal tissue. RNA sequencing libraries were prepared from 10 fresh frozen tumor samples, the 10 corresponding patient-derived cell lines, and 7 commercial cell lines. Our results identified alterations in tumor suppressor genes such as FBXW7, CDKN2A, CDKN2B, and MTAP, all known to drive MPM tumorigenesis. Patient-derived cell lines correlate to a high degree with their originating tumor. Gene expressions involved in multiple pathways such as EMT, apoptosis, myogenesis, and angiogenesis are upregulated in tumor samples when compared to patient-derived cell lines; however, they are downregulated in commercial cell lines compared to patient-derived cell lines, indicating significant differences between the two model systems. Our results show that the genome and transcriptome of tumors correlate to a higher degree with patient-derived cell lines rather than commercial cell lines. These results are of major relevance for the scientific community in regard to using cell lines as an appropriate model, resembling the pathway of interest to avoid misleading results for clinical applications.<\/jats:p>","DOI":"10.3390\/cancers15102813","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T07:03:58Z","timestamp":1684393438000},"page":"2813","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genomic and Transcriptomic Analyses of Malignant Pleural Mesothelioma (MPM) Samples Reveal Crucial Insights for Preclinical Testing"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4689-456X","authenticated-orcid":false,"given":"Alexander","family":"Laure","sequence":"first","affiliation":[{"name":"Faculty of Science and Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland"},{"name":"Faculty of Science, University of Zurich, CH-8006 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelica","family":"Rigutto","sequence":"additional","affiliation":[{"name":"Faculty of Science and Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland"},{"name":"Faculty of Science, University of Zurich, CH-8006 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7444-9829","authenticated-orcid":false,"given":"Michaela B.","family":"Kirschner","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, University Hospital Zurich, CH-8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lennart","family":"Opitz","sequence":"additional","affiliation":[{"name":"Functional Genomics Center Zurich, Swiss Federal Institute of Technology, University of Zurich, CH-8057 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Grob","sequence":"additional","affiliation":[{"name":"NEXUS Personalized Health Technologies, ETH Zurich, CH-8092 Zurich, Switzerland"},{"name":"Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5900-9040","authenticated-orcid":false,"given":"Isabelle","family":"Opitz","sequence":"additional","affiliation":[{"name":"Faculty of Science, University of Zurich, CH-8006 Zurich, Switzerland"},{"name":"Department of Thoracic Surgery, University Hospital Zurich, CH-8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3408-0294","authenticated-orcid":false,"given":"Emanuela","family":"Felley-Bosco","sequence":"additional","affiliation":[{"name":"Faculty of Science, University of Zurich, CH-8006 Zurich, Switzerland"},{"name":"Laboratory of Molecular Oncology, Department of Thoracic Surgery, University Hospital Zurich, CH-8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Hiltbrunner","sequence":"additional","affiliation":[{"name":"Faculty of Science and Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland"},{"name":"Department of Medical Oncology and Haematology, University Hospital Zurich, CH-8091 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Curioni-Fontecedro","sequence":"additional","affiliation":[{"name":"Faculty of Science and Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland"},{"name":"Department of Medical Oncology and Haematology, University Hospital Zurich, CH-8091 Zurich, Switzerland"},{"name":"Department of Oncology, HFR Fribourg-H\u00f4pital Cantonal, CH-1708 Fribourg, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0140-6736(20)32714-8","article-title":"First-Line Nivolumab Plus Ipilimumab in Unresectable Malignant Pleural Mesothelioma (Checkmate 743): A Multicentre, Randomised, Open-Label, Phase 3 Trial","volume":"397","author":"Baas","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S1470-2045(18)30765-4","article-title":"Nivolumab or Nivolumab Plus Ipilimumab in Patients with Relapsed Malignant Pleural Mesothelioma (Ifct-1501 Maps2): A Multicentre, Open-Label, Randomised, Non-Comparative, Phase 2 Trial","volume":"20","author":"Scherpereel","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3389\/fonc.2020.00187","article-title":"Immunotherapy in Malignant Pleural Mesothelioma","volume":"10","author":"Borm","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1136\/thoraxjnl-2020-216602","article-title":"Use of preclinical models for malignant pleural mesothelioma","volume":"76","author":"Shamseddin","year":"2021","journal-title":"Thorax"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"748444","DOI":"10.3389\/fonc.2021.748444","article-title":"Preclinical Models and Resources to Facilitate Basic Science Research on Malignant Mesothelioma\u2014A Review","volume":"11","author":"JJohnson","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1093\/jnci\/djt007","article-title":"The Clinical Relevance of Cancer Cell Lines","volume":"105","author":"Gillet","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.lungcan.2009.12.005","article-title":"Lung cancer cell lines: Useless artifacts or invaluable tools for medical science?","volume":"68","author":"Gazdar","year":"2010","journal-title":"Lung Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s13058-015-0613-0","article-title":"Assessing breast cancer cell lines as tumour models by comparison of mRNA expression profiles","volume":"17","author":"Vincent","year":"2015","journal-title":"Breast Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1186\/s12864-016-2911-z","article-title":"Comprehensive comparison of molecular portraits between cell lines and tumors in breast cancer","volume":"17","author":"Jiang","year":"2016","journal-title":"BMC Genom."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1038\/ncomms3126","article-title":"Evaluating cell lines as tumour models by comparison of genomic profiles","volume":"4","author":"Domcke","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.ccr.2006.03.030","article-title":"Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines","volume":"9","author":"Lee","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1186\/1755-8794-8-S2-S5","article-title":"Relating hepatocellular carcinoma tumor samples and cell lines using gene expression data in translational research","volume":"8","author":"Chen","year":"2015","journal-title":"BMC Med. Genom."},{"key":"ref_13","first-page":"4963","article-title":"Translation of microarray data into clinically relevant cancer diagnostic tests using gene expression ratios in lung cancer and mesothelioma","volume":"62","author":"Gordon","year":"2002","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1016\/S0002-9440(10)62492-3","article-title":"Identification of Novel Candidate Oncogenes and Tumor Suppressors in Malignant Pleural Mesothelioma Using Large-Scale Transcriptional Profiling","volume":"166","author":"Gordon","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100938","DOI":"10.1016\/j.xcrm.2023.100938","article-title":"Genomic and transcriptomic analyses identify a prognostic gene signature and predict response to therapy in pleural and peritoneal mesothelioma","volume":"4","author":"Nair","year":"2023","journal-title":"Cell Rep. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/cdd.2015.165","article-title":"Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease","volume":"23","author":"Chernova","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"63","DOI":"10.12688\/f1000research.16665.2","article-title":"Sarek: A Portable Workflow for Whole-Genome Sequencing Analysis of Germline and Somatic Variants","volume":"9","author":"Garcia","year":"2020","journal-title":"F1000Research"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/nbt.3820","article-title":"Nextflow enables reproducible computational workflows","volume":"35","author":"Chatzou","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kurtzer, G.M., Sochat, V., and Bauer, M.W. (2017). Singularity: Scientific containers for mobility of compute. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177459"},{"key":"ref_21","unstructured":"Li, H. (2013). Aligning Sequence Reads, Clone Sequences and Assembly Contigs with Bwa-Mem. arXiv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Talevich, E., Shain, A.H., Botton, T., and Bastian, B.C. (2016). CNVkit: Genome-Wide Copy Number Detection and Visualization from Targeted DNA Sequencing. PLoS Comput. Biol., 12.","DOI":"10.1371\/journal.pcbi.1004873"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1093\/bioinformatics\/btr670","article-title":"Control-FREEC: A tool for assessing copy number and allelic content using next-generation sequencing data","volume":"28","author":"Boeva","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1007\/s11626-015-9885-z","article-title":"Establishment of immortalized murine mesothelial cells and a novel mesothelioma cell line","volume":"51","author":"Blum","year":"2015","journal-title":"Vitr. Cell. Dev. Biol.-Anim."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/978-1-4939-9240-9_3","article-title":"Full-Length Single-Cell Rna Sequencing with Smart-Seq2","volume":"1979","author":"Picelli","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"Fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1093\/nar\/gkt214","article-title":"The Subread aligner: Fast, accurate and scalable read mapping by seed-and-vote","volume":"41","author":"Liao","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"EdgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_31","first-page":"187","article-title":"A Generic Methodology for Clustering to Maximises Inter-Cluster Inertia","volume":"8","author":"Alaoui","year":"2017","journal-title":"Int. J. Adv. Comput. Sci. Appl."},{"key":"ref_32","unstructured":"Kuettel, V., Pfister, S., and Ferrero, E. (2023, May 17). Deconvolution of Bulk Rna-Seq Data with Granulator. Available online: http:\/\/bioconductor.jp\/packages\/release\/bioc\/vignettes\/granulator\/inst\/doc\/granulator.html."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/j.celrep.2019.01.041","article-title":"RNA-Seq Signatures Normalized by mRNA Abundance Allow Absolute Deconvolution of Human Immune Cell Types","volume":"26","author":"Monaco","year":"2019","journal-title":"Cell Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (Msigdb) Hallmark Gene Set Collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/s41416-020-01178-9","article-title":"EMTome: A resource for pan-cancer analysis of epithelial-mesenchymal transition genes and signatures","volume":"124","author":"Vasaikar","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1038\/s41416-022-01979-0","article-title":"Genomic landscape of pleural and peritoneal mesothelioma tumours","volume":"127","author":"Hiltbrunner","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41568-018-0060-1","article-title":"The COSMIC Cancer Gene Census: Describing genetic dysfunction across all human cancers","volume":"18","author":"Sondka","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41580-018-0080-4","article-title":"New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer","volume":"20","author":"Dongre","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.cell.2008.03.027","article-title":"The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells","volume":"133","author":"Mani","year":"2008","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"R59","DOI":"10.1186\/bcr2896","article-title":"Epithelial to mesenchymal transition markers expressed in circulating tumour cells of early and metastatic breast cancer patients","volume":"13","author":"Kallergi","year":"2011","journal-title":"Breast Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1053\/j.gastro.2006.06.016","article-title":"A Transient, EMT-Linked Loss of Basement Membranes Indicates Metastasis and Poor Survival in Colorectal Cancer","volume":"131","author":"Spaderna","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1038\/s41388-018-0153-z","article-title":"How Asbestos Drives the Tissue towards Tumors: Yap Activation, Macrophage and Mesothelial Precursor Recruitment, Rna Editing, and Somatic Mutations","volume":"37","author":"Rehrauer","year":"2018","journal-title":"Oncogene"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"98280","DOI":"10.18632\/oncotarget.21550","article-title":"Gremlin-1 is a key regulator of the invasive cell phenotype in mesothelioma","volume":"8","author":"Yin","year":"2017","journal-title":"Oncotarget"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"34495","DOI":"10.18632\/oncotarget.26130","article-title":"Transglutaminase is a mesothelioma cancer stem cell survival protein that is required for tumor formation","volume":"9","author":"Adhikary","year":"2018","journal-title":"Oncotarget"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Wawruszak, A., Kalafut, J., Okon, E., Czapinski, J., Halasa, M., Przybyszewska, A., Miziak, P., Okla, K., Rivero-Muller, A., and Stepulak, A. (2019). Histone Deacetylase Inhibitors and Phenotypical Transformation of Cancer Cells. Cancers, 11.","DOI":"10.3390\/cancers11020148"},{"key":"ref_46","first-page":"6449","article-title":"Blood-Flow, Oxygen and Nutrient Supply, and Metabolic Microenvironment of Human-Tumors\u2014A Review","volume":"49","author":"Vaupel","year":"1989","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/nrc2501","article-title":"Hypoxia signalling through mTOR and the unfolded protein response in cancer","volume":"8","author":"Wouters","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7405","DOI":"10.1128\/MCB.22.21.7405-7416.2002","article-title":"Regulation of Protein Synthesis by Hypoxia via Activation of the Endoplasmic Reticulum Kinase Perk and Phosphorylation of the Translation Initiation Factor Eif2 Alpha","volume":"22","author":"Koumenis","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5650","DOI":"10.1038\/s41467-020-19015-1","article-title":"Benchmarking of cell type deconvolution pipelines for transcriptomics data","volume":"11","author":"Cobos","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s13059-021-02290-6","article-title":"A benchmark for RNA-seq deconvolution analysis under dynamic testing environments","volume":"22","author":"Jin","year":"2021","journal-title":"Genome Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1136\/thoraxjnl-2020-215027","article-title":"Patient-derived malignant pleural mesothelioma cell cultures: A tool to advance biomarker-driven treatments","volume":"75","author":"Kanellakis","year":"2020","journal-title":"Thorax"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"100039","DOI":"10.1016\/j.crmeth.2021.100039","article-title":"A pan-cancer survey of cell line tumor similarity by feature-weighted molecular profiles","volume":"1","author":"Sinha","year":"2021","journal-title":"Cell Rep. Methods"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"21272","DOI":"10.18632\/oncotarget.7114","article-title":"Identification of cis- and trans-acting elements regulating calretinin expression in mesothelioma cells","volume":"7","author":"Kapaklikaya","year":"2016","journal-title":"Oncotarget"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3389\/fgene.2017.00070","article-title":"Posttranscriptional Regulation Controls Calretinin Expression in Malignant Pleural Mesothelioma","volume":"8","author":"Sulemani","year":"2017","journal-title":"Front. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"977","DOI":"10.3892\/ol.2016.4685","article-title":"A novel alternative splicing isoform of NF2 identified in human Schwann cells","volume":"12","author":"Su","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"100036","DOI":"10.1016\/j.modpat.2022.100036","article-title":"Immunohistochemical Demonstration of Merlin\/NF2 Loss in Mesothelioma","volume":"36","author":"MMartin","year":"2023","journal-title":"Mod. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"100030","DOI":"10.1016\/j.modpat.2022.100030","article-title":"Neurofibromatosis Type 2-Yes-Associated Protein and Transcriptional Coactivator with PDZ-Binding Motif Dual Immunohistochemistry Is a Reliable Marker for the Detection of Neurofibromatosis Type 2 Alterations in Diffuse Pleural Mesothelioma","volume":"36","author":"Li","year":"2023","journal-title":"Mod. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/s41586-018-0409-3","article-title":"Genetic and transcriptional evolution alters cancer cell line drug response","volume":"560","author":"Siranosian","year":"2018","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s13073-021-00931-w","article-title":"Multi-Site Tumor Sampling Highlights Molecular Intra-Tumor Heterogeneity in Malignant Pleural Mesothelioma","volume":"13","author":"Meiller","year":"2021","journal-title":"Genome Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.celrep.2018.03.025","article-title":"Loss of Dnmt3a Immortalizes Hematopoietic Stem Cells In Vivo","volume":"23","author":"Jeong","year":"2018","journal-title":"Cell Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"68721","DOI":"10.18632\/oncotarget.11897","article-title":"Expression of a recombinant full-length LRP1B receptor in human non-small cell lung cancer cells confirms the postulated growth-suppressing function of this large LDL receptor family member","volume":"7","author":"Beer","year":"2016","journal-title":"Oncotarget"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"350","DOI":"10.21037\/tlcr.2017.06.06","article-title":"Targeting the epigenome in malignant pleural mesothelioma","volume":"6","author":"McLoughlin","year":"2017","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/sj.onc.1204106","article-title":"Muc4\/sialomucin complex, an intramembrane modulator of ErbB2\/HER2\/Neu, potentiates primary tumor growth and suppresses apoptosis in a xenotransplanted tumor","volume":"20","author":"Komatsu","year":"2001","journal-title":"Oncogene"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"101391","DOI":"10.1016\/j.smim.2020.101391","article-title":"MUCIN-4 (MUC4) is a novel tumor antigen in pancreatic cancer immunotherapy","volume":"47","author":"Gautam","year":"2020","journal-title":"Semin. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1757-2215-4-7","article-title":"MUC4 stabilizes HER2 expression and maintains the cancer stem cell population in ovarian cancer cells","volume":"4","author":"Ponnusamy","year":"2011","journal-title":"J. Ovarian Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"D923","DOI":"10.1093\/nar\/gky872","article-title":"Cell Model Passports\u2014A hub for clinical, genetic and functional datasets of preclinical cancer models","volume":"47","author":"Barthorpe","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/s41388-022-02577-3","article-title":"BAP1 loss induces mitotic defects in mesothelioma cells through BRCA1-dependent and independent mechanisms","volume":"42","author":"Singh","year":"2023","journal-title":"Oncogene"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.lungcan.2018.03.009","article-title":"Malignant cells from pleural fluids in malignant mesothelioma patients reveal novel mutations","volume":"119","author":"Sneddon","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1016\/j.celrep.2017.10.052","article-title":"Genetic and Genomic Characterization of 462 Melanoma Patient-Derived Xenografts, Tumor Biopsies, and Cell Lines","volume":"21","author":"Garman","year":"2017","journal-title":"Cell Rep."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ramundo, V., Zanirato, G., and Aldieri, E. (2021). The Epithelial-to-Mesenchymal Transition (EMT) in the Development and Metastasis of Malignant Pleural Mesothelioma. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212216"},{"key":"ref_71","first-page":"3200","article-title":"Antisense oligonucleotides specific for transforming growth factor beta2 inhibit the growth of malignant mesothelioma both in vitro and in vivo","volume":"57","author":"Marzo","year":"1997","journal-title":"Cancer Res."},{"key":"ref_72","first-page":"4479","article-title":"Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway","volume":"9","author":"Herbertz","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"26750","DOI":"10.1074\/jbc.M116.753236","article-title":"Malignant Pleural Effusion and Ascites Induce Epithelial-Mesenchymal Transition and Cancer Stem-Like Cell Properties via the Vascular Endothelial Growth Factor (Vegf)\/Phosphatidylinositol 3-Kinase (Pi3k)\/Akt\/Mechanistic Target of Rapamycin (Mtor) Pathway*","volume":"291","author":"Yin","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12967-016-0816-x","article-title":"Human lung adenocarcinoma cell cultures derived from malignant pleural effusions as model system to predict patients chemosensitivity","volume":"14","author":"Roscilli","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Basak, S.K., Veena, M.S., Oh, S., Huang, G., Srivatsan, E., Huang, M., Sharma, S., and Batra, R.K. (2009). The Malignant Pleural Effusion as a Model to Investigate Intratumoral Heterogeneity in Lung Cancer. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005884"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Mancini, R., Giarnieri, E., de Vitis, C., Malanga, N., Roscilli, G., Noto, A., Marra, E., Laudanna, C., Zoppoli, P., and De Luca, P. (2011). Spheres Derived from Lung Adenocarcinoma Pleural Effusions: Molecular Characterization and Tumor Engraftment. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021320"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1165\/ajrcmb.25.5.4539","article-title":"Histone Deacetylase Inhibitor Downregulation of bcl-xl Gene Expression Leads to Apoptotic Cell Death in Mesothelioma","volume":"25","author":"Cao","year":"2001","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1097\/JTO.0b013e318194f991","article-title":"A Histone Deacetylase Inhibitor LBH589 Downregulates XIAP in Mesothelioma Cell Lines Which is Likely Responsible for Increased Apoptosis with TRAIL","volume":"4","author":"Symanowski","year":"2009","journal-title":"J. Thorac. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.1158\/1078-0432.CCR-08-1579","article-title":"Valproate, in Combination with Pemetrexed and Cisplatin, Provides Additional Efficacy to the Treatment of Malignant Mesothelioma","volume":"15","author":"Vandermeers","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3923","DOI":"10.1200\/JCO.2005.14.167","article-title":"Phase I Study of an Oral Histone Deacetylase Inhibitor, Suberoylanilide Hydroxamic Acid, in Patients with Advanced Cancer","volume":"23","author":"Kelly","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1038\/nrc1235","article-title":"Comparative biology of mouse versus human cells: Modelling human cancer in mice","volume":"3","author":"Rangarajan","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/s41598-022-04973-x","article-title":"A panel of emerging EMT genes identified in malignant mesothelioma","volume":"12","author":"Wu","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Pardo-S\u00e1nchez, J.M., Manche\u00f1o, N., Cer\u00f3n, J., Jord\u00e1, C., Ansotegui, E., Juan, \u00d3., Palanca, S., Cremades, A., Gand\u00eda, C., and Farr\u00e0s, R. (2021). Increased Tumor Growth Rate and Mesenchymal Properties of Nsclc-Patient-Derived Xenograft Models During Serial Transplantation. Cancers, 13.","DOI":"10.3390\/cancers13122980"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"869485","DOI":"10.3389\/fonc.2022.869485","article-title":"An Orthotopic Patient-Derived Xenograft (PDX) Model Allows the Analysis of Metastasis-Associated Features in Colorectal Cancer","volume":"12","author":"Francescangeli","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_85","first-page":"181","article-title":"Transplantation of Human Malignant Mesothelioma into Nude Mice","volume":"40","author":"Chahinian","year":"1980","journal-title":"Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1158\/1078-0432.CCR-16-0844","article-title":"Patient-Derived Xenograft Establishment from Human Malignant Pleural Mesothelioma","volume":"23","author":"Wu","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1002\/jcp.26022","article-title":"Humanized mice: A brief overview on their diverse applications in biomedical research","volume":"233","author":"Fujiwara","year":"2018","journal-title":"J. Cell. Physiol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/10\/2813\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:37:29Z","timestamp":1760125049000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/10\/2813"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,18]]},"references-count":87,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["cancers15102813"],"URL":"https:\/\/doi.org\/10.3390\/cancers15102813","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2023,5,18]]}}}