High-Throughput Hybridization Assay as First-Line Diagnostic Test for Sarcomas: Clinical Assessment in a Tertiary Referral Center.
Context.--Sarcomas are rare and highly heterogeneous mesenchymal tumors with deceptive morphologic features that pose a challenge for precise diagnostics. Chromosomal rearrangements generating pathognomonic gene fusions are useful diagnostic markers, traditionally tested using single-plex standard o...
| Publicado en: | Archives of Pathology & Laboratory Medicine Vol. 149; no. 6; pp. 511 - 519 |
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| Autores principales: | , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
College of American Pathologists
Jun2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=185710496&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 185710496 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00039985 1FS jtl: Archives of Pathology & Laboratory Medicine issn: 00039985 maglogo: N pubinfo: dt: Jun2025 vid: 149 iid: 6 pid: 2550 pub: College of American Pathologists place: Northfield, Illinois artinfo: ui: 185710496 185710496 185710496 10.5858/arpa.2024-0202-OA 185710496 ppf: 511 ppct: 8 formats: fmt: @attributes: type: P tig: atl: High-Throughput Hybridization Assay as First-Line Diagnostic Test for Sarcomas: Clinical Assessment in a Tertiary Referral Center. aug: au: Salguero-Aranda, Carmen Perez, Marco Vargas-Padilla, María Victoria Beltrán-Povea, Amparo Delgado-Bellido, Daniel Marcilla, David Civantos, Gema de Álava, Enrique Díaz-Martín, Juan affil: Department of Pathology, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, CSIC-Universidad de Sevilla, Seville, Spain sug: subj: Tumor Markers, Biological Blood Genes Physiology High-Throughput Screening Assays Methods Sarcoma Diagnosis Sarcoma Familial and Genetic Sensitivity and Specificity Evaluation Tertiary Health Care Referral and Consultation Sarcoma Therapy Human Retrospective Design Record Review Validation Studies Genes Prospective Studies Gene Expression Profiling Neoplasm Grading Oncologic Care Standards Carrier Proteins Physiology Signal Transduction Physiology Transcription Factors Physiology Cyclic AMP Metabolism Descriptive Statistics Data Analysis Software ab: Context.--Sarcomas are rare and highly heterogeneous mesenchymal tumors with deceptive morphologic features that pose a challenge for precise diagnostics. Chromosomal rearrangements generating pathognomonic gene fusions are useful diagnostic markers, traditionally tested using single-plex standard of care assays with limited diagnostic yield. NanoString nCounter technology has emerged as a robust solution with multiplexing capabilities. Objective.--To optimize NanoString effective coverage of specific entities and conduct a validation study to support its clinical implementation. Design.--We reconfigured a NanoString codeset by including a set of probes for detecting gene fusion variants of solitary fibrous tumors, low-grade fibromyxoid sarcomas/sclerosing epithelioid fibrosarcomas, and undifferentiated small round cell sarcomas, totaling 188 probes. A technical validation study was conducted with 96 retrospective samples. Additionally, 76 prospective samples were evaluated to assess the assay's clinical performance. Results.--Both technical and clinical validation studies showed that NanoString's codeset reached >88% sensitivity and 100% specificity, compared with standard of care methods, and superior diagnostic yield as a first-line test. Our design enabled the detection of almost all fusion variants of NGFI-A binding protein 2 (NAB2) with signal transducer and activator of transcription 6 (STAT6) in solitary fibrous tumors, as well as cAMP responsive element binding protein 3 like 1/2 (CREB3L1/2) rearrangements in all low-grade fibromyxoid sarcoma/sclerosing epithelioid fibrosarcoma cases. Identification of specific gene fusions of undifferentiated small round cell sarcoma was also improved, but additional strategies are necessary to attain full coverage. Conclusions.--The NanoString platform demonstrated good sensitivity, specificity, and superior diagnostic yield. It is a cost-effective assay with rapid turnaround time, low sample consumption, streamlined analysis, and easy customization. Therefore, it is a promising alternative first-line diagnostic tool for routine sarcoma testing. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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