The current study assessed the performance of the fully automated RT-PCR-based Idylla™ GeneFusion Assay, which simultaneously covers the advanced non-small cell lung carcinoma (aNSCLC) actionable ALK, ROS1, RET, and MET exon 14 rearrangements, in a routine clinical setting involving 12 European clinical centers. The Idylla™ GeneFusion Assay detects fusions using fusion-specific as well as expression imbalance detection, the latter enabling detection of uncommon fusions not covered by fusion-specific assays. In total, 326 archival aNSCLC formalin-fixed paraffin-embedded (FFPE) samples were included of which 44% were resected specimen, 46% tissue biopsies, and 9% cytological specimen. With a total of 179 biomarker-positive cases (i.e., 85 ALK, 33 ROS1, 20 RET fusions and 41 MET exon 14 skipping), this is one of the largest fusion-positive datasets ever tested. The results of the Idylla™ GeneFusion Assay were compared with earlier results of routine reference technologies including fluorescence in situ hybridization, immunohistochemistry, reverse-transcription polymerase chain reaction, and next-generation sequencing, establishing a high sensitivity/specificity of 96.1%/99.6% for ALK, 96.7%/99.0% for ROS1, 100%/99.3% for RET fusion, and 92.5%/99.6% for MET exon 14 skipping, and a low failure rate (0.9%). The Idylla™ GeneFusion Assay was found to be a reliable, sensitive, and specific tool for routine detection of ALK, ROS1, RET fusions and MET exon 14 skipping. Given its short turnaround time of about 3 h, it is a time-efficient upfront screening tool in FFPE samples, supporting rapid clinical decision making. Moreover, expression-imbalance-based detection of potentially novel fusions may be easily verified with other routine technologies without delaying treatment initiation.

Bavarian Cancer Research Center Erlangen Germany

Bioptická Laboratoř Pilsen Czechia

Cabinet de Pathologie Cypath Lyon France

Centro de Investigación Biomédica en Red de Cáncer Madrid Spain

Complejo Hospitalario de A Coruña Corunna Spain

Comprehensive Cancer Center Erlangen EMN Erlangen Germany

Copenhagen Denmark

Department of Clinical and Molecular Medicine Pathology Unit St Andrea University Hospital University of Rome La Sapienza Rome Italy

Department of Pathology Luzerner Kantonsspital Lucerne Switzerland

Department of Pathology Rigshospitalet University Hospital of Copenhagen Copenhagen Denmark

FHU OncoAge IHU RespirERA Hôpital Pasteur Centre Hospitalier Universitaire de Nice Université Côte d'Azur Nice France

Hospital integrated Biobank Hôpital Pasteur Nice France

Institut de Pathologie et de Génétique Gosselies Belgium

Institut für Pathologie Klinikum Kassel Kassel Germany

Institute of Pathology University Erlangen Nürnberg Erlangen Germany

Laboratory of Clinical and Experimental Pathology Hôpital Pasteur Centre Hospitalier Universitaire de Nice Université Côte d'Azur Nice France

Molecular Pathology Group Department of Pathology Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana Madrid Spain

UF de Pathologie Centre Jean Perrin INSERM U1240 Clermont Ferrand France

Virchows Arch. 2024 Nov;485(5):959. doi: 10.1007/s00428-024-03800-0. PubMed

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