{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:37:06Z","timestamp":1786534626784,"version":"build-2736575974"},"reference-count":64,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PRONON","award":["25000.019858\/2018-14"],"award-info":[{"award-number":["25000.019858\/2018-14"]}]},{"name":"National Science and Technology Institute for Children\u2019s Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Brazil","award":["406484\/2022-8"],"award-info":[{"award-number":["406484\/2022-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Soft tissue sarcomas (STSs) are a heterogeneous group of rare mesenchymal malignancies with overlapping morphological and immunohistochemical features, often making definitive diagnosis challenging. Recent advances in next-generation sequencing (NGS) have enabled the identification of recurrent molecular alterations that contribute to tumor classification, prognostic stratification, and precision oncology approaches. This retrospective study aimed to evaluate the diagnostic and clinical impact of molecular profiling in pediatric soft tissue sarcomas using the Oncomine Childhood Cancer Research Assay (OCCRA) panel. Fifty-five frozen tumor samples representing 24 distinct soft tissue sarcoma subtypes were obtained from the Pediatric Oncology Institute -IOP\/GRAACC\/UNIFESP Biobank (B-053). Molecular analysis was performed using NGS to identify gene fusions, single nucleotide variants (SNVs), copy number variations (CNVs), and insertions\/deletions (InDels). Clinically relevant molecular alterations were identified in 70% (37\/55) of cases, including 18 fusion transcripts, 13 SNVs, 8 CNVs, and 6 InDels. Recurrent and diagnostically relevant alterations included BCOR::CCNB3, ASPSCR1::TFE3, NFR1::BRAF, FUS::DDIT3, EML4::NTRK3, ETV6::NTRK3, CIC::DUX4, NAB2::STAT6 and SS18::SSX1\/2 fusions, as well as amplifications involving PDGFRA, FGFR1, GLI1, CDK4, ERBB3, and KIT. Pathogenic variants affecting genes involved in tumor suppression and chromatin remodeling, including TP53, NF1, DICER1, SMARCA4, PTEN, and PIK3CA, were also detected. Importantly, molecular profiling had significant diagnostic impact in several histologically ambiguous tumors, enabling molecular reclassification and refinement of previously inconclusive or inaccurate pathological diagnoses. In multiple cases, NGS transformed descriptive histopathological interpretations into genetically defined sarcoma entities, including NTRK-rearranged spindle cell neoplasms, CIC-rearranged sarcomas, synovial sarcoma, low-grade fibromyxoid sarcoma, and clear cell sarcoma. Furthermore, the identification of actionable alterations highlighted potential opportunities for targeted therapies and precision medicine approaches. Our findings demonstrate that comprehensive molecular profiling significantly enhances diagnostic accuracy in pediatric soft tissue sarcomas, particularly in morphologically challenging cases. The integration of NGS into routine sarcoma diagnostics enables biologically informed tumor classification and supports personalized therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms27167201","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:02:11Z","timestamp":1786532531000},"page":"7201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Next-Generation Sequencing Refines Diagnosis and Expands Precision Medicine Opportunities in Soft Tissue Sarcomas"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2959-8363","authenticated-orcid":false,"given":"Francine","family":"Tesser-Gamba","sequence":"first","affiliation":[{"name":"Genetics Laboratory, Pediatric Oncology Institute (IOP\/GRAACC), Federal University of Sao Paulo, Sao Paulo 04039-001, SP, Brazil"},{"name":"National Science and Technology Institute for Children\u2019s Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90010-150, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0114-4578","authenticated-orcid":false,"given":"Thais Biude","family":"Mendes","sequence":"additional","affiliation":[{"name":"Genetics Laboratory, Pediatric Oncology Institute (IOP\/GRAACC), Federal University of Sao Paulo, Sao Paulo 04039-001, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Teresa","family":"Lima","sequence":"additional","affiliation":[{"name":"Genetics Laboratory, Pediatric Oncology Institute (IOP\/GRAACC), Federal University of Sao Paulo, Sao Paulo 04039-001, SP, Brazil"},{"name":"Department of Gynecology, Federal University of Sao Paulo, Sao Paulo 04024-002, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9675-0380","authenticated-orcid":false,"given":"Simone de Campos Vieira","family":"Abib","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Pediatric Oncology Institute (IOP\/GRAACC), Federal University of Sao Paulo, Sao Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana Maria Monteiro","family":"Caran","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Pediatric Oncology Institute (IOP\/GRAACC), Federal University of Sao Paulo, Sao Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Regina Caminada de","family":"Toledo","sequence":"additional","affiliation":[{"name":"Genetics Laboratory, Pediatric Oncology Institute (IOP\/GRAACC), Federal University of Sao Paulo, Sao Paulo 04039-001, SP, Brazil"},{"name":"National Science and Technology Institute for Children\u2019s Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90010-150, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","unstructured":"WHO Classification of Tumours Editorial Board (2020). Soft Tissue and Bone Tumours, International Agency for Research on Cancer. [5th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155406","DOI":"10.1016\/j.prp.2024.155406","article-title":"Pathogenetic and molecular classifications of soft tissue and bone tumors: A 2024 update","volume":"260","author":"Gurzu","year":"2024","journal-title":"Pathol. Res. Pract."},{"key":"ref_3","first-page":"109937","article-title":"WHO classification of soft tissue tumours: An update based on the 2020 edition","volume":"56","author":"Jo","year":"2024","journal-title":"Pathology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Choi, J.H., and Ro, J.Y. (2023). The Recent Advances in Molecular Diagnosis of Soft Tissue Tumors. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065934"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s00428-024-03736-5","article-title":"Current challenges and practical aspects of molecular pathology for bone and soft tissue tumors","volume":"484","year":"2024","journal-title":"Virchows Arch."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1007\/s00256-024-04584-9","article-title":"Recent advances in molecular profiling of bone and soft tissue tumors","volume":"53","author":"Baumhoer","year":"2024","journal-title":"Skelet. Radiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"31","DOI":"10.33545\/26649063.2024.v6.i1a.19","article-title":"Molecular pathology in the diagnosis and classification of soft tissue sarcomas","volume":"6","author":"Kabugo","year":"2024","journal-title":"Int. J. Pathol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e23196","DOI":"10.1002\/gcc.23196","article-title":"Complementary value of molecular analysis to expert review in refining classification of uncommon soft tissue tumors","volume":"63","author":"Suurmeijer","year":"2024","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.cancergen.2025.10.106","article-title":"Current state of diagnostic genetic testing in pediatric sarcoma: Survey and review by the Cancer Genomics Consortium Sarcoma Working Group","volume":"298\u2013299","author":"Schieffer","year":"2025","journal-title":"Cancer Genet."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Frazzette, N., and Jour, G. (2025). Novel molecular methods in soft tissue sarcomas: From diagnostics to theragnostics. Cancers, 17.","DOI":"10.3390\/cancers17071215"},{"key":"ref_11","first-page":"472","article-title":"Comprehensive genomic profiling refines diagnosis and reveals clinically relevant alterations in pediatric soft tissue sarcomas","volume":"31","author":"Zhou","year":"2026","journal-title":"Diagn. Pathol."},{"key":"ref_12","first-page":"325","article-title":"New advances in the molecular classification of pediatric mesenchymal tumors","volume":"476","author":"Suurmeijer","year":"2019","journal-title":"Virchows Arch."},{"key":"ref_13","first-page":"109","article-title":"Unravelling undifferentiated soft tissue sarcomas: Insights from genomics","volume":"80","author":"Nottley","year":"2022","journal-title":"Hispathology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1097\/PAS.0000000000001203","article-title":"Expanding the spectrum of pediatric NTRK-rearranged mesenchymal tumors","volume":"43","author":"Davis","year":"2019","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S1470-2045(18)30119-0","article-title":"Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: Phase 1 results from a multicentre, open-label, phase 1\/2 study","volume":"19","author":"Laetsch","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"a003848","DOI":"10.1101\/mcs.a003848","article-title":"Urothelial carcinoma with NRF1\u2013BRAF rearrangement and response to targeted therapy","volume":"5","author":"Isaacson","year":"2019","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1158\/1078-0432.CCR-13-1081","article-title":"Molecular pathways: Adaptive kinome reprogramming in response to targeted inhibition of the BRAF\u2013MEK\u2013ERK pathway in cancer","volume":"20","author":"Johnson","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"70","DOI":"10.32074\/1591-951X-213","article-title":"The 2020 WHO Classification of Soft Tissue Tumours: News and perspectives","volume":"113","author":"Sbaraglia","year":"2021","journal-title":"Pathologica"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1749-799X-6-15","article-title":"The clinical significance of the FUS\u2013CREB3L2 translocation in low-grade fibromyxoid sarcoma","volume":"6","author":"Rose","year":"2011","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5755","DOI":"10.1038\/sj.onc.1204601","article-title":"Fusions of the SYT and SSX genes in synovial sarcoma","volume":"20","author":"Ladanyi","year":"2001","journal-title":"Oncogene"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/gcc.22835","article-title":"A morphologic and molecular reappraisal of myoepithelial tumors of soft tissue, bone, and viscera with EWSR1 and FUS gene rearrangements","volume":"59","author":"Suurmeijer","year":"2020","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s12105-015-0618-0","article-title":"Myoepithelial neoplasms of soft tissue: An updated review of the clinicopathologic, immunophenotypic, and genetic features","volume":"9","author":"Jo","year":"2015","journal-title":"Head Neck Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1097\/PAS.0b013e31814b18fb","article-title":"Clear cell sarcoma of soft tissue: A clinicopathologic, immunohistochemical, and molecular analysis of 33 cases","volume":"32","author":"Hisaoka","year":"2008","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_24","first-page":"263","article-title":"Clear cell sarcoma: Morphology and genetics of a distinctive soft tissue neoplasm","volume":"18","author":"Thway","year":"2014","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1097\/PAS.0000000000000846","article-title":"Sarcomas with CIC-rearrangements are a distinct pathologic entity with aggressive outcome: A clinicopathologic and molecular study of 115 cases","volume":"41","author":"Antonescu","year":"2017","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/gcc.20945","article-title":"High prevalence of CIC fusion with double homeobox (DUX4) transcription factors in CIC-rearranged round cell sarcomas","volume":"51","author":"Italiano","year":"2012","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nature13109","article-title":"C11orf95-RELA fusions drive oncogenic NF-\u03baB signalling in ependymoma","volume":"506","author":"Parker","year":"2014","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/neup.12770","article-title":"Ependymosarcoma harboring C11orf95:RELA fusion transcript: Report of two cases and review of the literature","volume":"41","author":"Mahajan","year":"2021","journal-title":"Neuropathology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13045-024-01580-3","article-title":"New strategies in soft tissue sarcoma treatment","volume":"17","author":"Ghazzi","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"105577","DOI":"10.1016\/j.esmoop.2025.105577","article-title":"Exploring the impact of NGS on diagnostics and treatment of sarcoma: Insights from real-world data across multiple institutions in Europe","volume":"10","author":"Kyriazoglou","year":"2025","journal-title":"ESMO Open"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Remiszewski, P., Bobak, K., Pi\u0105tkowski, J., Golik, P., Tysarowski, A., Seliga, K., Spa\u0142ek, M.J., Szumera-Cie\u0107kiewicz, A., W\u0105grodzki, M., and Rutkowski, P. (2026). Detection of Gene Fusions in Soft Tissue Sarcoma Using Next-Generation Sequencing. Genes, 17.","DOI":"10.3390\/genes17050514"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"184","DOI":"10.4132\/jptm.2023.03.20","article-title":"What\u2019s new in bone and soft tissue pathology 2023: Guidelines for molecular testing","volume":"57","author":"Obeidin","year":"2023","journal-title":"J. Pathol. Transl. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez-Jimeno, M., Alba-Pav\u00f3n, P., Astigarraga, I., Im\u00edzcoz, T., Panizo-Morgado, E., Garc\u00eda-Obreg\u00f3n, S., Catal\u00e1n-Lamb\u00e1n, A., San-Juli\u00e1n, M., Lamo-Espinosa, J.M., and Echebarria-Barona, A. (2021). Clinical Value of NGS Genomic Studies for Clinical Management of Pediatric and Young Adult Bone Sarcomas. Cancers, 13.","DOI":"10.3390\/cancers13215436"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1001\/jamaoncol.2025.3608","article-title":"Guidelines for Next-Generation Sequencing in Sarcoma Diagnosis and Treatment: A Consensus Review","volume":"11","author":"Serrano","year":"2025","journal-title":"JAMA Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41571-018-0113-0","article-title":"NTRK fusion-positive cancers and TRK inhibitor therapy","volume":"15","author":"Cocco","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1056\/NEJMoa1714448","article-title":"Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children","volume":"378","author":"Drilon","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_37","first-page":"7012","article-title":"Fusion of the FUS and CREB3L2 genes in low-grade fibromyxoid sarcoma","volume":"63","author":"Storlazzi","year":"2003","journal-title":"Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1056\/NEJM199801153380303","article-title":"SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma","volume":"338","author":"Kawai","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1097\/PAS.0000000000000570","article-title":"CIC-rearranged sarcomas: A study of 20 cases and comparisons with Ewing sarcomas","volume":"40","author":"Yoshida","year":"2016","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1002\/gcc.20491","article-title":"EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma","volume":"46","author":"Antonescu","year":"2007","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/ng.1107","article-title":"A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion","volume":"44","author":"Pierron","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1158\/2159-8290.CD-15-0443","article-title":"An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101","volume":"5","author":"Doebele","year":"2015","journal-title":"Cancer Discov."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1001\/jamaoncol.2016.0264","article-title":"Progression-Free Survival Among Patients with Well-Differentiated or Dedifferentiated Liposarcoma Treated with the CDK4 Inhibitor Palbociclib: A Phase 2 Clinical Trial","volume":"2","author":"Dickson","year":"2016","journal-title":"JAMA Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1097\/01.pas.0000170343.09562.39","article-title":"MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: A comparative analysis of 559 soft tissue neoplasms with genetic data","volume":"29","author":"Binh","year":"2005","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1158\/2159-8290.CD-15-0894","article-title":"Targeting CDK4 and CDK6: From Discovery to Therapy","volume":"6","author":"Sherr","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2984","DOI":"10.1101\/gad.12.19.2984","article-title":"Tumor surveillance via the ARF-p53 pathway","volume":"12","author":"Sherr","year":"1998","journal-title":"Genes Dev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3453","DOI":"10.1093\/nar\/26.15.3453","article-title":"The MDM2 gene amplification database","volume":"26","author":"Momand","year":"1998","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nrc3430","article-title":"MDM2, MDMX and p53 in oncogenesis and cancer therapy","volume":"13","author":"Wade","year":"2013","journal-title":"Nat. Rev. Cancer."},{"key":"ref_49","first-page":"355","article-title":"HER3 signaling and targeted therapy in cancer","volume":"12","author":"Mishra","year":"2018","journal-title":"Oncol. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1093\/jnci\/djs501","article-title":"HER3 overexpression and survival in solid tumors: A meta-analysis","volume":"105","author":"Ocana","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.tcb.2007.06.007","article-title":"The Gli code: An information nexus regulating cell fate, stemness and cancer","volume":"17","author":"Mas","year":"2007","journal-title":"Trends Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Pietrobono, S., Gagliardi, S., and Stecca, B. (2019). Non-canonical Hedgehog signaling pathway in cancer: Activation of GLI transcription factors beyond Smoothened. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00556"},{"key":"ref_53","unstructured":"Cancer Genome Atlas Research Network (2017). Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas. Cell, 171, 950\u2013965.e28."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6336","DOI":"10.1158\/1078-0432.CCR-14-1293","article-title":"Analysis of 1,115 patients tested for MET amplification and therapy response in the MD Anderson Phase I Clinic","volume":"20","author":"Jardim","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1158\/1078-0432.CCR-17-3089","article-title":"DICER1 and associated conditions: Identification of at-risk individuals and recommended surveillance strategies","volume":"24","author":"Schultz","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","article-title":"The PI3K pathway in human disease","volume":"170","author":"Fruman","year":"2017","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/nrm3330","article-title":"The functions and regulation of the PTEN tumour suppressor","volume":"13","author":"Song","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12943-023-01827-6","article-title":"PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer","volume":"22","author":"Glaviano","year":"2023","journal-title":"Mol. Cancer."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/bjc.2013.281","article-title":"Functional and cancer genomics of ASXL family members","volume":"109","author":"Katoh","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"15293","DOI":"10.1007\/s00432-023-05277-x","article-title":"Inhibitors of the PI3K\/AKT\/mTOR pathway in human malignancies: Trend of current clinical trials","volume":"149","author":"Delshad","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1038\/s41591-023-02321-8","article-title":"Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: The phase 2 ROAR trial","volume":"29","author":"Subbiah","year":"2023","journal-title":"Nat. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"viii16","DOI":"10.1093\/annonc\/mdz384","article-title":"Identifying patients with NTRK fusion cancer","volume":"30","author":"Solomon","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_63","first-page":"85","article-title":"Molecular profiling of osteosarcoma in children and adolescents from different age groups using a next-generation sequencing panel","volume":"258\u2013259","author":"Petrilli","year":"2021","journal-title":"Cancer Genet."},{"key":"ref_64","unstructured":"Thermo Fisher Scientific (2018). Oncomine\u2122 Childhood Cancer Research Assay User Guide, Thermo Fisher Scientific. Publication No. MAN0017117."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7201\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:04:16Z","timestamp":1786532656000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":64,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167201"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167201","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]}}}