{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T04:05:17Z","timestamp":1762056317740,"version":"build-2065373602"},"reference-count":105,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T00:00:00Z","timestamp":1656028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["CA148805","CA06927","HHSN261201500003I"],"award-info":[{"award-number":["CA148805","CA06927","HHSN261201500003I"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Cancer Institute (NCI)","award":["CA148805","CA06927","HHSN261201500003I"],"award-info":[{"award-number":["CA148805","CA06927","HHSN261201500003I"]}]},{"name":"National Institutes of Health (NIH)","award":["CA148805","CA06927","HHSN261201500003I"],"award-info":[{"award-number":["CA148805","CA06927","HHSN261201500003I"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Malignant mesothelioma (MMe) is a rare malignancy originating from the linings of the pleural, peritoneal and pericardial cavities. The best-defined risk factor is exposure to carcinogenic mineral fibers (e.g., asbestos). Genomic studies have revealed that the most frequent genetic lesions in human MMe are mutations in tumor suppressor genes. Several genetically engineered mouse models have been generated by introducing the same genetic lesions found in human MMe. However, most of these models require specialized breeding facilities and long-term exposure of mice to asbestos for MMe development. Thus, an alternative model with high tumor penetrance without asbestos is urgently needed. We characterized an orthotopic model using MMe cells derived from Cdkn2a+\/\u2212;Nf2+\/\u2212 mice chronically injected with asbestos. These MMe cells were tumorigenic upon intraperitoneal injection. Moreover, MMe cells showed mixed chromosome and microsatellite instability, supporting the notion that genomic instability is relevant in MMe pathogenesis. In addition, microsatellite markers were detectable in the plasma of tumor-bearing mice, indicating a potential use for early cancer detection and monitoring the effects of interventions. This orthotopic model with rapid development of MMe without asbestos exposure represents genomic instability and specific molecular targets for therapeutic or preventive interventions to enable preclinical proof of concept for the intervention in an immunocompetent setting.<\/jats:p>","DOI":"10.3390\/cancers14133108","type":"journal-article","created":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T10:39:13Z","timestamp":1656153553000},"page":"3108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mesothelioma Mouse Models with Mixed Genomic States of Chromosome and Microsatellite Instability"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7151-0575","authenticated-orcid":false,"given":"Yurong","family":"Song","sequence":"first","affiliation":[{"name":"Cancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8905-5048","authenticated-orcid":false,"given":"Shaneen S.","family":"Baxter","sequence":"additional","affiliation":[{"name":"Cancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisheng","family":"Dai","sequence":"additional","affiliation":[{"name":"Cancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chelsea","family":"Sanders","sequence":"additional","affiliation":[{"name":"Animal Research Technical Support of Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Burkett","sequence":"additional","affiliation":[{"name":"Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1658-7569","authenticated-orcid":false,"given":"Ryan N.","family":"Baugher","sequence":"additional","affiliation":[{"name":"CLIA Molecular Diagnostics Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie D.","family":"Mellott","sequence":"additional","affiliation":[{"name":"CLIA Molecular Diagnostics Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd B.","family":"Young","sequence":"additional","affiliation":[{"name":"CLIA Molecular Diagnostics Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi E.","family":"Lawhorn","sequence":"additional","affiliation":[{"name":"CLIA Molecular Diagnostics Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Difilippantonio","sequence":"additional","affiliation":[{"name":"Animal Research Technical Support of Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baktiar","family":"Karim","sequence":"additional","affiliation":[{"name":"Molecular Histopathology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuwaraj","family":"Kadariya","sequence":"additional","affiliation":[{"name":"Cancer Signaling and Epigenetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ligia A.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Cancer ImmunoPrevention Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1301-5175","authenticated-orcid":false,"given":"Joseph R.","family":"Testa","sequence":"additional","affiliation":[{"name":"Cancer Signaling and Epigenetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert H.","family":"Shoemaker","sequence":"additional","affiliation":[{"name":"Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1093\/carcin\/bgt166","article-title":"Molecular pathogenesis of malignant mesothelioma","volume":"34","author":"Sekido","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/cncr.10923","article-title":"The use of CDKN2A deletion as a diagnostic marker for malignant mesothelioma in body cavity effusions","volume":"99","author":"Illei","year":"2003","journal-title":"Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10854","DOI":"10.1073\/pnas.92.24.10854","article-title":"High frequency of inactivating mutations in the neurofibromatosis type 2 gene (NF2) in primary malignant mesotheliomas","volume":"92","author":"Bianchi","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.lungcan.2008.08.014","article-title":"Functional inactivation of NF2\/merlin in human mesothelioma","volume":"64","author":"Thurneysen","year":"2009","journal-title":"Lung Cancer"},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/ng.912","article-title":"Germline BAP1 mutations predispose to malignant mesothelioma","volume":"43","author":"Testa","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1097\/JTO.0000000000000471","article-title":"High Incidence of Somatic BAP1 alterations in sporadic malignant mesothelioma","volume":"10","author":"Nasu","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_8","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_9","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_10","doi-asserted-by":"crossref","first-page":"8090","DOI":"10.1158\/0008-5472.CAN-05-2312","article-title":"A mouse model recapitulating molecular features of human mesothelioma","volume":"65","author":"Altomare","year":"2005","journal-title":"Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4388","DOI":"10.1158\/0008-5472.CAN-14-1328","article-title":"Germline mutation of Bap1 accelerates development of asbestos-induced malignant mesothelioma","volume":"74","author":"Xu","year":"2014","journal-title":"Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Altomare, D.A., Menges, C.W., Xu, J., Pei, J., Zhang, L., Tadevosyan, A., Neumann-Domer, E., Liu, Z., Carbone, M., and Chudoba, I. (2011). Losses of both products of the Cdkn2a\/Arf locus contribute to asbestos-induced mesothelioma development and cooperate to accelerate tumorigenesis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018828"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1158\/0008-5472.CAN-15-3371","article-title":"Bap1 Is a Bona Fide Tumor Suppressor: Genetic Evidence from Mouse Models Carrying Heterozygous Germline Bap1 Mutations","volume":"76","author":"Kadariya","year":"2016","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1038\/onc.2015.243","article-title":"Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma","volume":"35","author":"Napolitano","year":"2016","journal-title":"Oncogene"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sneddon, S., Patch, A.M., Dick, I.M., Kazakoff, S., Pearson, J.V., Waddell, N., Allcock, R.J.N., Holt, R.A., Robinson, B.W.S., and Creaney, J. (2017). Whole exome sequencing of an asbestos-induced wild-type murine model of malignant mesothelioma. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3382-6"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/nrc.2017.42","article-title":"Novel insights into mesothelioma biology and implications for therapy","volume":"17","author":"Yap","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/j.jtho.2018.08.2036","article-title":"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","volume":"13","author":"Tsao","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1007\/s00262-011-1103-6","article-title":"Immune responses and immunotherapeutic interventions in malignant pleural mesothelioma","volume":"60","author":"Bograd","year":"2011","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1007\/s00262-011-1073-8","article-title":"Chronic inflammation in tumor stroma is an independent predictor of prolonged survival in epithelioid malignant pleural mesothelioma patients","volume":"60","author":"Suzuki","year":"2011","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1080\/17476348.2019.1563488","article-title":"Immunotherapy strategies for mesothelioma - the role of tumor specific neoantigens in a new era of precision medicine","volume":"13","author":"Ye","year":"2019","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1158\/1078-0432.CCR-21-1466","article-title":"FDA Approval Summary: Nivolumab in Combination with Ipilimumab for the Treatment of Unresectable Malignant Pleural Mesothelioma","volume":"28","author":"Nakajima","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_22","first-page":"263","article-title":"Mesothelioma dose response following intraperitoneal injection of mineral fibres","volume":"72","author":"Davis","year":"1991","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/sj.cgt.7700594","article-title":"Regression of AK7 malignant mesothelioma established in immunocompetent mice following intratumoral gene transfer of interferon gamma","volume":"10","author":"Valeyrie","year":"2003","journal-title":"Cancer Gene Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/0013-9351(84)90136-1","article-title":"Malignant mesothelioma induced by asbestos and zeolite in the mouse peritoneal cavity","volume":"35","author":"Suzuki","year":"1984","journal-title":"Environ. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3389\/fonc.2020.00101","article-title":"Preclinical Models of Malignant Mesothelioma","volume":"10","author":"Testa","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_26","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":"Johnson","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.ccr.2008.01.030","article-title":"A conditional mouse model for malignant mesothelioma","volume":"13","author":"Jongsma","year":"2008","journal-title":"Cancer Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8952","DOI":"10.1002\/jcp.26830","article-title":"Inactivation of Tp53 and Pten drives rapid development of pleural and peritoneal malignant mesotheliomas","volume":"233","author":"Sementino","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4113","DOI":"10.1158\/0008-5472.CAN-18-4093","article-title":"Inactivation of Bap1 Cooperates with Losses of Nf2 and Cdkn2a to Drive the Development of Pleural Malignant Mesothelioma in Conditional Mouse Models","volume":"79","author":"Kukuyan","year":"2019","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Badhai, J., Pandey, G.K., Song, J.Y., Krijgsman, O., Bhaskaran, R., Chandrasekaran, G., Kwon, M.C., Bombardelli, L., Monkhorst, K., and Grasso, C. (2020). Combined deletion of Bap1, Nf2, and Cdkn2ab causes rapid onset of malignant mesothelioma in mice. J Exp. Med., 217.","DOI":"10.1084\/jem.20191257"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1158\/0008-5472.CAN-13-2062","article-title":"Tumor suppressor alterations cooperate to drive aggressive mesotheliomas with enriched cancer stem cells via a p53-miR-34a-c-Met axis","volume":"74","author":"Menges","year":"2014","journal-title":"Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1002\/ijc.2910520609","article-title":"Establishment of a murine model of malignant mesothelioma","volume":"52","author":"Davis","year":"1992","journal-title":"Int. J. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1399-0039.2009.01275.x","article-title":"Chemoimmunotherapy: An emerging strategy for the treatment of malignant mesothelioma","volume":"74","author":"McCoy","year":"2009","journal-title":"Tissue Antigens"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1158\/0008-5472.CAN-14-1008","article-title":"Whole-exome sequencing reveals frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1 in malignant pleural mesothelioma","volume":"75","author":"Guo","year":"2015","journal-title":"Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6501","DOI":"10.1038\/onc.2017.266","article-title":"Inhibition of the spindle assembly checkpoint kinase Mps-1 as a novel therapeutic strategy in malignant mesothelioma","volume":"36","author":"Szymiczek","year":"2017","journal-title":"Oncogene"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Song, Y., Sullivan, T., Klarmann, K., Gilbert, D., O\u2019Sullivan, T.N., Lu, L., Wang, S., Haines, D.C., Van Dyke, T., and Keller, J.R. (2017). RB inactivation in keratin 18 positive thymic epithelial cells promotes non-cell autonomous T cell hyperproliferation in genetically engineered mice. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171510"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nature24673","article-title":"Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth","volume":"552","author":"Germano","year":"2017","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1002\/mc.22213","article-title":"Detection of coding microsatellite frameshift mutations in DNA mismatch repair-deficient mouse intestinal tumors","volume":"54","author":"Woerner","year":"2015","journal-title":"Mol. Carcinog."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6152928","DOI":"10.1155\/2018\/6152928","article-title":"Microsatellite Instability in Mouse Models of Colorectal Cancer","volume":"2018","author":"Currey","year":"2018","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/mc.20146","article-title":"Use of mononucleotide repeat markers for detection of microsatellite instability in mouse tumors","volume":"44","author":"Bacher","year":"2005","journal-title":"Mol. Carcinog."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Bacher, J.W., Sievers, C.K., Albrecht, D.M., Grimes, I.C., Weiss, J.M., Matkowskyj, K.A., Agni, R.M., Vyazunova, I., Clipson, L., and Storts, D.R. (2015). Improved Detection of Microsatellite Instability in Early Colorectal Lesions. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132727"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s12539-020-00358-8","article-title":"DNA Mismatch Repair Deficiency Detection in Colorectal Cancer by a New Microsatellite Instability Analysis System","volume":"12","author":"Wu","year":"2020","journal-title":"Interdiscip. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/ng1196-312","article-title":"Multicolour spectral karyotyping of mouse chromosomes","volume":"14","author":"Liyanage","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/BF00319691","article-title":"A system of nomenclature for band patterns of mouse chromosomes","volume":"41","author":"Nesbitt","year":"1973","journal-title":"Chromosoma"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"589929","DOI":"10.3389\/fimmu.2020.589929","article-title":"TERT-Regulation and Roles in Cancer Formation","volume":"11","author":"Dratwa","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6172","DOI":"10.1038\/s41388-019-0872-9","article-title":"Mechanisms underlying the activation of TERT transcription and telomerase activity in human cancer: Old actors and new players","volume":"38","author":"Yuan","year":"2019","journal-title":"Oncogene"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"282","DOI":"10.20892\/j.issn.2095-3941.2019.0437","article-title":"Role of the mechanical microenvironment in cancer development and progression","volume":"17","author":"Liu","year":"2020","journal-title":"Cancer Biol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"940","DOI":"10.3389\/fimmu.2020.00940","article-title":"The Tumor Microenvironment: A Milieu Hindering and Obstructing Antitumor Immune Responses","volume":"11","author":"Loskog","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"R921","DOI":"10.1016\/j.cub.2020.06.081","article-title":"The tumor microenvironment","volume":"30","author":"Anderson","year":"2020","journal-title":"Curr. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.3892\/or.2016.4660","article-title":"Role of the tumor microenvironment in tumor progression and the clinical applications (Review)","volume":"35","author":"Yuan","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.pbiomolbio.2011.06.006","article-title":"The role of the microenvironment in tumor growth and invasion","volume":"106","author":"Kim","year":"2011","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"608406","DOI":"10.1155\/2012\/608406","article-title":"Immune microenvironment in tumor progression: Characteristics and challenges for therapy","volume":"2012","author":"Chew","year":"2012","journal-title":"J. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5904","DOI":"10.1038\/onc.2008.271","article-title":"The tumor microenvironment and its role in promoting tumor growth","volume":"27","author":"Whiteside","year":"2008","journal-title":"Oncogene"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.17.00073","article-title":"Landscape of Microsatellite Instability Across 39 Cancer Types","volume":"2017","author":"Bonneville","year":"2017","journal-title":"JCO Precis. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.jtcvs.2018.10.039","article-title":"Treatment of malignant pleural mesothelioma with chemotherapy preceding versus after surgical resection","volume":"157","author":"Verma","year":"2019","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/S0140-6736(15)01238-6","article-title":"Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): A randomised, controlled, open-label, phase 3 trial","volume":"387","author":"Zalcman","year":"2016","journal-title":"Lancet"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.rmed.2018.06.026","article-title":"A systematic review and meta-analysis of second-line therapies for treatment of mesothelioma","volume":"141","author":"Petrelli","year":"2018","journal-title":"Respir. Med."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Rovers, S., Janssens, A., Raskin, J., Pauwels, P., van Meerbeeck, J.P., Smits, E., and Marcq, E. (2022). Recent Advances of Immune Checkpoint Inhibition and Potential for (Combined) TIGIT Blockade as a New Strategy for Malignant Pleural Mesothelioma. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030673"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1111\/j.1440-1746.2012.07200.x","article-title":"Molecular pathways in colorectal cancer","volume":"27","author":"Biankin","year":"2012","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.2174\/1389450111007011341","article-title":"Targeting karyotypic complexity and chromosomal instability of cancer cells","volume":"11","author":"Roschke","year":"2010","journal-title":"Curr. Drug Targets"},{"key":"ref_62","first-page":"589","article-title":"Genomic Instability and Cancer","volume":"5","author":"Yao","year":"2014","journal-title":"J. Carcinog. Mutagen"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1056\/NEJMra0804588","article-title":"Molecular origins of cancer: Molecular basis of colorectal cancer","volume":"361","author":"Markowitz","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_64","first-page":"5418","article-title":"High frequency of micronuclei in peripheral blood lymphocytes as index of susceptibility to pleural malignant mesothelioma","volume":"62","author":"Bolognesi","year":"2002","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/cncr.11398","article-title":"Detection of numerical aberrations of chromosomes 7 and 9 in cytologic specimens of pleural malignant mesothelioma","volume":"99","author":"Shin","year":"2003","journal-title":"Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1510\/icvts.2008.201509","article-title":"Chromosomal deletion in patients with malignant pleural mesothelioma","volume":"9","author":"Sugarbaker","year":"2009","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_67","first-page":"4349","article-title":"Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma","volume":"53","author":"Taguchi","year":"1993","journal-title":"Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1002\/ijc.23949","article-title":"Genomic events associated with progression of pleural malignant mesothelioma","volume":"124","author":"Ivanov","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/gcc.2870110104","article-title":"Loss of heterozygosity on the short arm of chromosome 3 in mesothelioma cell lines and solid tumors","volume":"11","author":"Zeiger","year":"1994","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1111\/j.1349-7006.2006.00386.x","article-title":"Genomic profiling of malignant pleural mesothelioma with array-based comparative genomic hybridization shows frequent non-random chromosomal alteration regions including JUN amplification on 1p32","volume":"98","author":"Taniguchi","year":"2007","journal-title":"Cancer Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0165-4608(90)90258-C","article-title":"Cytogenetic analysis of malignant mesothelioma","volume":"47","author":"Hagemeijer","year":"1990","journal-title":"Cancer Genet. Cytogenet."},{"key":"ref_72","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_73","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/path.1128","article-title":"Molecular cytogenetic differences between histological subtypes of malignant mesotheliomas: DNA cytometry and comparative genomic hybridization of 90 cases","volume":"197","author":"Krismann","year":"2002","journal-title":"J. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.1158\/0008-5472.CAN-18-3235","article-title":"Chromosomal Instability in Tumor Initiation and Development","volume":"79","author":"Bach","year":"2019","journal-title":"Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/ng1861","article-title":"A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers","volume":"38","author":"Carter","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1056\/NEJMoa1616288","article-title":"Tracking the Evolution of Non-Small-Cell Lung Cancer","volume":"376","author":"Wilson","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/0092-8674(90)90186-I","article-title":"A genetic model for colorectal tumorigenesis","volume":"61","author":"Fearon","year":"1990","journal-title":"Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"520","DOI":"10.3332\/ecancer.2015.520","article-title":"Biology of colorectal cancer","volume":"9","author":"Arvelo","year":"2015","journal-title":"Ecancermedicalscience"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.1038\/onc.2013.365","article-title":"The MutSbeta complex is a modulator of p53-driven tumorigenesis through its functions in both DNA double-strand break repair and mismatch repair","volume":"33","author":"Edwards","year":"2014","journal-title":"Oncogene"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s13073-021-00958-z","article-title":"Profiling diverse sequence tandem repeats in colorectal cancer reveals co-occurrence of microsatellite and chromosomal instability involving Chromosome 8","volume":"13","author":"Shin","year":"2021","journal-title":"Genome Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1016\/j.jtho.2018.07.015","article-title":"Mismatch Repair Protein Defects and Microsatellite Instability in Malignant Pleural Mesothelioma","volume":"13","author":"Arulananda","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Gilson, P., Merlin, J.L., and Harle, A. (2021). Detection of Microsatellite Instability: State of the Art and Future Applications in Circulating Tumour DNA (ctDNA). Cancers, 13.","DOI":"10.3390\/cancers13071491"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/386623a0","article-title":"Genetic instability in colorectal cancers","volume":"386","author":"Lengauer","year":"1997","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1016\/S0002-9440(10)63500-6","article-title":"Chromosomal imbalances in the colorectal carcinomas with microsatellite instability","volume":"163","author":"Li","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.1111\/j.1572-0241.2006.00845.x","article-title":"Microsatellite instability accounts for tumor site-related differences in clinicopathologic variables and prognosis in human colon cancers","volume":"101","author":"Sinicrope","year":"2006","journal-title":"Am. J. Gastroenterol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"6379","DOI":"10.1158\/1078-0432.CCR-06-1248","article-title":"Chromosomal instability in microsatellite-unstable and stable colon cancer","volume":"12","author":"Trautmann","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s10142-016-0532-x","article-title":"DNA copy number profiling in microsatellite-stable and microsatellite-unstable hereditary non-polyposis colorectal cancers by targeted CNV array","volume":"17","author":"Chen","year":"2017","journal-title":"Funct. Integr. Genom."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Ali, H., Bitar, M.S., Al Madhoun, A., Marafie, M., and Al-Mulla, F. (2017). Functionally-focused algorithmic analysis of high resolution microarray-CGH genomic landscapes demonstrates comparable genomic copy number aberrations in MSI and MSS sporadic colorectal cancer. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171690"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13073-017-0434-0","article-title":"Multilevel genomics of colorectal cancers with microsatellite instability-clinical impact of JAK1 mutations and consensus molecular subtype 1","volume":"9","author":"Sveen","year":"2017","journal-title":"Genome Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.neo.2018.07.007","article-title":"Characterizing Microsatellite Instability and Chromosome Instability in Interval Colorectal Cancers","volume":"20","author":"Cisyk","year":"2018","journal-title":"Neoplasia"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1373\/clinchem.2014.223677","article-title":"Microsatellite instability detection by next generation sequencing","volume":"60","author":"Salipante","year":"2014","journal-title":"Clin. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"7452","DOI":"10.18632\/oncotarget.13918","article-title":"Performance evaluation for rapid detection of pan-cancer microsatellite instability with MANTIS","volume":"8","author":"Kautto","year":"2017","journal-title":"Oncotarget"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"7035","DOI":"10.1158\/1078-0432.CCR-19-1324","article-title":"Validation of Microsatellite Instability Detection Using a Comprehensive Plasma-Based Genotyping Panel","volume":"25","author":"Willis","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"12880","DOI":"10.1038\/s41598-021-91974-x","article-title":"Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer","volume":"11","author":"Dedeurwaerdere","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"a029611","DOI":"10.1101\/cshperspect.a029611","article-title":"Chromosomal Instability as a Driver of Tumor Heterogeneity and Evolution","volume":"7","author":"Bakhoum","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_96","first-page":"2061183","article-title":"Current treatments for inoperable mesothelioma: Indirect comparisons based on individual patient data reconstructed retrospectively from 4 trials","volume":"2022","author":"Messori","year":"2022","journal-title":"J. Chemother."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e221490","DOI":"10.1001\/jamanetworkopen.2022.1490","article-title":"Comparison of 3 Randomized Clinical Trials of Frontline Therapies for Malignant Pleural Mesothelioma","volume":"5","author":"Meirson","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_98","first-page":"100280","article-title":"A Real-World Analysis of the Use of Systemic Therapy in Malignant Pleural Mesothelioma and the Differential Impacts on Overall Survival by Practice Pattern","volume":"3","author":"Kerrigan","year":"2022","journal-title":"JTO Clin. Res. Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1002\/(SICI)1097-0215(19981209)78:6<740::AID-IJC12>3.0.CO;2-5","article-title":"Primary human mesothelioma cells express class II MHC, ICAM-1 and B7-2 and can present recall antigens to autologous blood lymphocytes","volume":"78","author":"Mutti","year":"1998","journal-title":"Int. J. Cancer"},{"key":"ref_100","first-page":"161","article-title":"Transforming growth factor-beta released by PPD-presenting malignant mesothelioma cells inhibits interferon-gamma synthesis by an anti-PPD CD4+ T-cell clone","volume":"11","author":"Valle","year":"2003","journal-title":"Int. J. Mol. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1158\/2159-8290.CD-20-0790","article-title":"DNA Polymerase and Mismatch Repair Exert Distinct Microsatellite Instability Signatures in Normal and Malignant Human Cells","volume":"11","author":"Chung","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1053\/j.gastro.2010.08.001","article-title":"Microsatellite alterations at selected tetranucleotide repeats are associated with morphologies of colorectal neoplasias","volume":"139","author":"Lee","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/bjc.2014.167","article-title":"Prevalence and implications of elevated microsatellite alterations at selected tetranucleotides in cancer","volume":"111","author":"Watson","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11888-017-0352-y","article-title":"Microsatellite Instability Pathway and EMAST in Colorectal Cancer","volume":"13","author":"Carethers","year":"2017","journal-title":"Curr. Colorectal Cancer Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"13764","DOI":"10.1038\/s41598-018-32057-2","article-title":"A new method for discovering EMAST sequences in animal models of cancer","volume":"8","author":"Bhaskaran","year":"2018","journal-title":"Sci. Rep."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/13\/3108\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:39:49Z","timestamp":1760139589000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/13\/3108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,24]]},"references-count":105,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["cancers14133108"],"URL":"https:\/\/doi.org\/10.3390\/cancers14133108","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2022,6,24]]}}}