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Multicenter Study
. 2024 Apr;484(4):677-686.
doi: 10.1007/s00428-024-03778-9. Epub 2024 Mar 16.

Multicenter evaluation of an automated, multiplex, RNA-based molecular assay for detection of ALK, ROS1, RET fusions and MET exon 14 skipping in NSCLC

Linea Melchior  1   2 , Astrid Hirschmann  3 , Paul Hofman  4   5   6 , Christophe Bontoux  4   5   6 , Angel Concha  7 , Salima Mrabet-Dahbi  8 , Pascal Vannuffel  9 , Emmanuel Watkin  10 , Martina Putzová  11 , Stefania Scarpino  12 , Anne Cayre  13 , Paloma Martin  14   15 , Robert Stoehr  16   17   18 , Arndt Hartmann  16   17   18
Affiliations
Multicenter Study

Multicenter evaluation of an automated, multiplex, RNA-based molecular assay for detection of ALK, ROS1, RET fusions and MET exon 14 skipping in NSCLC

Linea Melchior et al. Virchows Arch. 2024 Apr.

Erratum in

Abstract

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.

Keywords: ALK fusion; MET exon 14 skipping; RET fusion; ROS1 fusion; Idylla; NSCLC.

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Conflict of interest statement

Bontoux Christophe: nothing to declare

Cayre Anne: nothing to declare

Concha Angel: nothing to declare

Hartmann Arndt: honoraria for lectures or consulting/advisory boards for Abbvie, Agilent, AstraZeneca, Biocartis, BMS, Boehringer Ingelheim, Cepheid, Diaceutics, Gilead, Illumina, Ipsen, Janssen, Lilly, Merck, MSD, Nanostring, Novartis, Pfizer, Qiagen, QUIP GmbH, Roche, Sanofi, 3DHistotech and other research support from AstraZeneca, Biocartis, Cepheid, Gilead, Illumina, Janssen, Nanostring, Novartis, Owkin, Qiagen, QUIP GmbH, Roche, Sanofi

Hirschmann Astrid: nothing to declare

Hofman Paul: member of the Biocartis advisory board

Martin Paloma: nothing to declare

Melchior Linea: nothing to declare

Mrabet-Dahbi Salima: nothing to declare

Putzová Martina: nothing to declare

Scarpino Stefania: nothing to declare

Stoehr Robert: nothing to declare

Vannuffel Pascal: nothing to declare

Watkin Emmanuel: honoraria for lectures or consulting/advisory boards for AstraZeneca, Janssen, MSD, Incyte, Pierre Fabre

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