{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:23:11Z","timestamp":1760145791006,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T00:00:00Z","timestamp":1725321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Molecular profiles of thymomas and recurrent thymomas are far from being defined. Herein, we report an analysis of a comprehensive genetic profile (CGP) in a highly selected cohort of recurrent thymomas. Among a cohort of 426 thymomas, the tissue was available in 23 recurrent tumors for matching the biomolecular results obtained from primary and relapse samples. A control group composed of non-recurrent thymoma patients was selected through a propensity score match analysis. CGP was performed using the NGS Tru-SightOncology assay to evaluate TMB, MSI, and molecular alterations in 523 genes. CGP does not differ when comparing initial tumor with tumor relapse. A significantly higher frequency of cell cycle control genes alterations (100.0% vs. 57.1%, p = 0.022) is detected in patients with early recurrence (&lt;32 months) compared to late recurrent cases. The CGPs were similar in recurrent thymomas and non-recurrent thymomas. Finally, based on NGS results, an off-label treatment or clinical trial could be potentially proposed in &gt;50% of cases (oncogenic Tier-IIC variants). In conclusion, CGPs do not substantially differ between initial tumor vs. tumor recurrence and recurrent thymomas vs. non-recurrent thymomas. Cell cycle control gene alterations are associated with an early recurrence after thymectomy. Multiple target therapies are potentially available by performing a comprehensive CGP, suggesting that a precision medicine approach on these patients could be further explored.<\/jats:p>","DOI":"10.3390\/ijms25179560","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T12:22:33Z","timestamp":1725366153000},"page":"9560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Analysis of Comprehensive Genomic Profile in Thymomas and Recurrent Thymomas Reveals Potentially Actionable Mutations for Target Therapies"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9383-5554","authenticated-orcid":false,"given":"Filippo","family":"Lococo","sequence":"first","affiliation":[{"name":"Thoracic Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Thoracic Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"De Paolis","sequence":"additional","affiliation":[{"name":"Clinical Chemistry, Biochemistry and Molecular Biology Operations (UOC), Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Departmental Unit of Molecular and Genomic Diagnostics, Genomics Core Facility, Gemelli Science and Technology Park (G-STeP), Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Evangelista","sequence":"additional","affiliation":[{"name":"Thoracic Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Thoracic Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Dell\u2019Amore","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35122 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6085-1195","authenticated-orcid":false,"given":"Diana","family":"Giannarelli","sequence":"additional","affiliation":[{"name":"Epidemiology and Biostatistics Facility, Gemelli Science and Technology Park (G-STeP), Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3807-6911","authenticated-orcid":false,"given":"Marco","family":"Chiappetta","sequence":"additional","affiliation":[{"name":"Thoracic Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalisa","family":"Campanella","sequence":"additional","affiliation":[{"name":"Thoracic Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Sassorossi","sequence":"additional","affiliation":[{"name":"Thoracic Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Cancellieri","sequence":"additional","affiliation":[{"name":"Unit of Pathology, Fondazione Policlinico Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiorella","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35122 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Conca","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35122 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuele","family":"Vita","sequence":"additional","affiliation":[{"name":"UOSD Oncologia Toraco-Polmonare, Comprehensive Cancer Center, Fondazione Policlinico Universitario Ago-stino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0833-4334","authenticated-orcid":false,"given":"Angelo","family":"Minucci","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35122 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilio","family":"Bria","sequence":"additional","affiliation":[{"name":"UOSD Oncologia Toraco-Polmonare, Comprehensive Cancer Center, Fondazione Policlinico Universitario Ago-stino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"UOC Oncologia Medica, Ospedale Isola Tiberina\u2014Gemelli Isola, 00186 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Castello","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Urbani","sequence":"additional","affiliation":[{"name":"Clinical Chemistry, Biochemistry and Molecular Biology Operations (UOC), Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Rea","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35122 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Margaritora","sequence":"additional","affiliation":[{"name":"Thoracic Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Thoracic Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Scambia","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ejca.2007.11.004","article-title":"Thymic Epithelial Tumours: A Population-Based Study of the Incidence, Diagnostic Procedures and Therapy","volume":"44","author":"Blaauwgeers","year":"2008","journal-title":"Eur. J. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1097\/JTO.0000000000000654","article-title":"The 2015 World Health Organization Classification of Tumors of the Thymus Continuity and Changes","volume":"10","author":"Marx","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/S0022-5223(96)70265-9","article-title":"Prognostic Factors and Long-Term Results after Thymoma Resection: A Series of 307 Patients","volume":"112","author":"Regnard","year":"1996","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1097\/JTO.0000000000000370","article-title":"Long-Term Results after Treatment for Recurrent Thymoma: A Multicenter Analysis","volume":"9","author":"Sandri","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_5","first-page":"894","article-title":"Single-Centre 40-Year Results of Redo Operation for Recurrent Thymomas","volume":"40","author":"Margaritora","year":"2011","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1016\/j.jtho.2021.07.004","article-title":"The International Thymic Malignancy Interest Group Classification of Thymoma Recurrence: Survival Analysis and Perspectives","volume":"16","author":"Chiappetta","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1097\/JTO.0000000000000378","article-title":"Surgical Management of Recurrent Thymic Epithelial Tumors: A Retrospective Analysis Based on the Japanese Nationwide Database","volume":"10","author":"Mizuno","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Chiappetta, M., Grossi, U., Sperduti, I., Margaritora, S., Marulli, G., Fiorelli, A., Sandri, A., Mizuno, T., Cusumano, G., and Hamaji, M. (2021). Which Is the Best Treatment in Recurrent Thymoma? A Systematic Review and Meta-Analysis. Cancers, 13.","DOI":"10.3390\/cancers13071559"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1097\/01.coc.0000227481.36109.e7","article-title":"Systemic Treatment of Malignant Thymoma: A Decade Experience at a Single Institution","volume":"29","author":"Giaccone","year":"2006","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1016\/j.athoracsur.2011.07.078","article-title":"Management and Outcomes of Relapse after Treatment for Thymoma and Thymic Carcinoma","volume":"92","author":"Bott","year":"2011","journal-title":"Ann. Thorac. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"707","DOI":"10.21037\/tlcr-22-794","article-title":"Genetic Profile of Thymic Epithelial Tumors in the Japanese Population: An Exploratory Study Examining Potential Therapeutic Targets","volume":"12","author":"Shimada","year":"2023","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101627","DOI":"10.1016\/j.esmoop.2023.101627","article-title":"Genomic Characterization of Thymic Epithelial Tumors in a Real-World Dataset","volume":"8","author":"Kurokawa","year":"2023","journal-title":"ESMO Open"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1093\/oncolo\/oyac115","article-title":"Comprehensive Genomic Profiling of 274 Thymic Epithelial Tumors Unveils Oncogenic Pathways and Predictive Biomarkers","volume":"27","author":"Girard","year":"2022","journal-title":"Oncologist"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Agrafiotis, A.C., Brand\u00e3o, M., Berghmans, T., Durieux, V., and Jungels, C. (2023). Immunotherapy and Targeted Therapies Efficacy in Thymic Epithelial Tumors: A Systematic Review. Biomedicines, 11.","DOI":"10.3390\/biomedicines11102722"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.jtho.2019.10.018","article-title":"A Recurrence Predictive Model for Thymic Tumors and Its Implication for Postoperative Management: A Chinese Alliance for Research in Thymomas Database Study","volume":"15","author":"Liu","year":"2020","journal-title":"J. Thorac. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.jtho.2024.04.004","article-title":"Survival Outcome After Surgery in Patients with Thymoma Distant Recurrence","volume":"19","author":"Chiappetta","year":"2024","journal-title":"J. Thorac. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1177\/1078155220968150","article-title":"Nivolumab Treatment for Metastatic Thymic Epithelial Tumors","volume":"27","author":"Ak","year":"2021","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5093","DOI":"10.21037\/jtd-21-290","article-title":"The Efficacy and Safety of Immunotherapy in Thymic Epithelial Tumors: More Effective, More Risky: A Systematic Review","volume":"13","author":"Song","year":"2021","journal-title":"J. Thorac. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Montella, L., Ottaviano, M., Morra, R., Pietroluongo, E., De Placido, P., Tortora, M., Sorrentino, C., Facchini, G., De Placido, S., and Giuliano, M. (2022). The Never-Ending History of Octreotide in Thymic Tumors: A Vintage or A Contemporary Drug?. Cancers, 14.","DOI":"10.3390\/cancers14030774"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e001075","DOI":"10.1136\/esmoopen-2020-001075","article-title":"First Results of the EORTC-SPECTA\/Arcagen Study Exploring the Genomics of Rare Cancers in Collaboration with the European Reference Network EURACAN","volume":"5","author":"Morfouace","year":"2020","journal-title":"ESMO Open"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Morfouace, M., Novello, S., Stevovic, A., Dooms, C., Jan\u017ei\u010d, U., Berghmans, T., Dziadziuszko, R., Gorlia, T., Felip, E., and Paz-Ares, L. (2022). Results of Screening in Early and Advanced Thoracic Malignancies in the EORTC Pan-European SPECTAlung Platform. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-12056-0"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7561","DOI":"10.21037\/jtd-2019-thym-13","article-title":"Correlation of Genomic Alterations and PD-L1 Expression in Thymoma","volume":"12","author":"Jovanovic","year":"2020","journal-title":"J. Thorac. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102014","DOI":"10.1016\/j.ctrv.2020.102014","article-title":"Thymic Epithelial Tumors: From Biology to Treatment","volume":"86","author":"Conforti","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e78","DOI":"10.1634\/theoncologist.2020-0509","article-title":"Cyclin Pathway Genomic Alterations Across 190,247 Solid Tumors: Leveraging Large-Scale Data to Inform Therapeutic Directions","volume":"26","author":"Jardim","year":"2021","journal-title":"Oncologist"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5078","DOI":"10.1158\/1078-0432.CCR-05-0070","article-title":"Analysis of Cell Cycle Regulator Proteins in Encapsulated Thymomas","volume":"11","author":"Baldi","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8519","DOI":"10.1200\/JCO.2018.36.15_suppl.8519","article-title":"Efficacy of Milciclib (PHA-848125AC), a Pan-Cyclin d-Dependent Kinase Inhibitor, in Two Phase II Studies with Thymic Carcinoma (TC) and B3 Thymoma (B3T) Patients","volume":"36","author":"Besse","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.jtho.2017.01.028","article-title":"Loss of P16INK4A Expression and Homozygous CDKN2A Deletion Are Associated with Worse Outcome and Younger Age in Thymic Carcinomas","volume":"12","author":"Aesif","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"ref_28","unstructured":"(2024, August 06). CBioPortal for Cancer Genomics. Available online: https:\/\/www.cbioportal.org\/."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.2741\/3780","article-title":"Regulation of MDM4","volume":"16","author":"Markey","year":"2011","journal-title":"Front. Biosci. (Landmark Ed)"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.athoracsur.2012.12.017","article-title":"BRCA1 Gene Mutation in Thymic Malignant Melanoma","volume":"96","author":"Yi","year":"2013","journal-title":"Ann. Thorac. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/gcc.20225","article-title":"Familial Occurrence of Thymoma and Autoimmune Diseases with the Constitutional Translocation t(14;20)(Q24.1;P12.3)","volume":"44","author":"Geffroy","year":"2005","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s12253-016-0144-8","article-title":"Molecular Profiling of Thymoma and Thymic Carcinoma: Genetic Differences and Potential Novel Therapeutic Targets","volume":"23","author":"Enkner","year":"2017","journal-title":"Pathol. Oncol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1634\/theoncologist.2019-0393","article-title":"Metastatic Thymoma Harboring a Deleterious BRCA2 Mutation Derives Durable Clinical Benefit from Olaparib","volume":"25","author":"Principe","year":"2020","journal-title":"Oncologist"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.aanat.2007.05.003","article-title":"Immunohistochemical Expression of Vascular Endothelial Growth Factor A (VEGF), and Its Receptors (VEGFR1, 2) in Normal and Pathologic Conditions of the Human Thymus","volume":"190","author":"Cimpean","year":"2008","journal-title":"Ann. Anat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S1470-2045(14)71181-7","article-title":"Sunitinib in Patients with Chemotherapy-Refractory Thymoma and Thymic Carcinoma: An Open-Label Phase 2 Trial","volume":"16","author":"Thomas","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/bjc.2015.425","article-title":"A Large MicroRNA Cluster on Chromosome 19 Is a Transcriptional Hallmark of WHO Type A and AB Thymomas","volume":"114","author":"Radovich","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S1470-2045(13)70596-5","article-title":"Cixutumumab for Patients with Recurrent or Refractory Advanced Thymic Epithelial Tumours: A Multicentre, Open-Label, Phase 2 Trial","volume":"15","author":"Rajan","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1200\/JCO.2017.74.4078","article-title":"Phase II Study of Everolimus in Patients with Thymoma and Thymic Carcinoma Previously Treated with Cisplatin-Based Chemotherapy","volume":"36","author":"Zucali","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Abu Zaid, M.I., Radovich, M., Althouse, S., Liu, H., Spittler, A.J., Solzak, J., Badve, S., and Loehrer, P.J. (2022). A Phase II Study of Buparlisib in Relapsed or Refractory Thymomas. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.891383"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Piana, D., Iavarone, F., De Paolis, E., Daniele, G., Parisella, F., Minucci, A., Greco, V., and Urbani, A. (2024). Phenotyping Tumor Heterogeneity through Proteogenomics: Study Models and Challenges. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25168830"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/j.1440-1827.1994.tb02936.x","article-title":"A Review of 79 Thymomas: Modification of Staging System and Reappraisal of Conventional Division into Invasive and Non-Invasive Thymoma","volume":"44","author":"Koga","year":"1994","journal-title":"Pathol. Int."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Brierley, J.D., Gospodarowicz, M.K., and Wittekind, C. (2017). TNM Classification of Malignant Tumours, Union for International Cancer Control. [8th ed.].","DOI":"10.1002\/9780471420194.tnmc26.pub3"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1097\/JTO.0000000000000154","article-title":"ITMIG Consensus Statement on the Use of the WHO Histological Classification of Thymoma and Thymic Carcinoma: Refined Definitions, Histological Criteria, and Reporting","volume":"9","author":"Marx","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41586-023-06045-0","article-title":"A Genomic Mutational Constraint Map Using Variation in 76,156 Human Genomes","volume":"625","author":"Chen","year":"2023","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"D1210","DOI":"10.1093\/nar\/gkad986","article-title":"COSMIC: A Curated Database of Somatic Variants and Clinical Data for Cancer","volume":"52","author":"Sondka","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1158\/2159-8290.CD-23-0467","article-title":"Quantifying the Expanding Landscape of Clinical Actionability for Patients with Cancer","volume":"14","author":"Suehnholz","year":"2024","journal-title":"Cancer Discov."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.17.00011","article-title":"OncoKB: A Precision Oncology Knowledge Base","volume":"1","author":"Chakravarty","year":"2017","journal-title":"JCO Precis. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D1062","DOI":"10.1093\/nar\/gkx1153","article-title":"ClinVar: Improving Access to Variant Interpretations and Supporting Evidence","volume":"46","author":"Landrum","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jmoldx.2016.10.002","article-title":"Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists","volume":"19","author":"Li","year":"2017","journal-title":"J. Mol. Diagn."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.annonc.2022.12.003","article-title":"Germline-Focused Analysis of Tumour-Detected Variants in 49,264 Cancer Patients: ESMO Precision Medicine Working Group Recommendations","volume":"34","author":"Kuzbari","year":"2023","journal-title":"Ann. Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9560\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:47:59Z","timestamp":1760111279000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9560"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,3]]},"references-count":50,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms25179560"],"URL":"https:\/\/doi.org\/10.3390\/ijms25179560","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,9,3]]}}}