JTO Clinical and Research Reports (Feb 2023)

Ultrafast Gene Fusion Assessment for Nonsquamous NSCLC

  • Véronique Hofman, MD, PhD,
  • Simon Heeke, PhD,
  • Christophe Bontoux, MD,
  • Lara Chalabreysse, MD,
  • Marc Barritault, MD, PhD,
  • Pierre Paul Bringuier, DVM,
  • Tanguy Fenouil, MD, PhD,
  • Nazim Benzerdjeb, MD, PhD,
  • Hugues Begueret, MD, PhD,
  • Jean Philippe Merlio, MD, PhD,
  • Charline Caumont, MD,
  • Nicolas Piton, MD, PhD,
  • Jean-Christophe Sabourin, MD, PhD,
  • Solène Evrard, MD, PhD,
  • Charlotte Syrykh, MD,
  • Anna Vigier, MD,
  • Pierre Brousset, MD, PhD,
  • Julien Mazieres, MD, PhD,
  • Elodie Long-Mira, MD, PhD,
  • Jonathan Benzaquen, MD, PhD,
  • Jacques Boutros, MD,
  • Maryline Allegra, PhD,
  • Virginie Tanga, MSc,
  • Virginie Lespinet-Fabre, PhD,
  • Myriam Salah, MSc,
  • Christelle Bonnetaud, MSc,
  • Olivier Bordone, MSc,
  • Sandra Lassalle, MD, PhD,
  • Charles-Hugo Marquette, MD, PhD,
  • Marius Ilié, MD, PhD,
  • Paul Hofman, MD, PhD

Journal volume & issue
Vol. 4, no. 2
p. 100457

Abstract

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Introduction: Gene fusion testing of ALK, ROS1, RET, NTRK, and MET exon 14 skipping mutations is guideline recommended in nonsquamous NSCLC (NS-NSCLC). Nevertheless, assessment is often hindered by the limited availability of tissue and prolonged next-generation sequencing (NGS) testing, which can protract the initiation of a targeted therapy. Therefore, the development of faster gene fusion assessment is critical for optimal clinical decision-making. Here, we compared two ultrafast gene fusion assays (UFGFAs) using NGS (Genexus, Oncomine Precision Assay, Thermo Fisher Scientific) and a multiplex reverse-transcriptase polymerase chain reaction (Idylla, GeneFusion Assay, Biocartis) approach at diagnosis in a retrospective series of 195 NS-NSCLC cases and five extrapulmonary tumors with a known NTRK fusion. Methods: A total of 195 NS-NSCLC cases (113 known gene fusions and 82 wild-type tumors) were included retrospectively. To validate the detection of a NTRK fusion, we added five NTRK-positive extrathoracic tumors. The diagnostic performance of the two UFGFAs and standard procedures was compared. Results: The accuracy was 92.3% and 93.1% for Idylla and Genexus, respectively. Both systems improved the sensitivity for detection by including a 5′-3′ imbalance analysis. Although detection of ROS1, MET exon 14 skipping, and RET was excellent with both systems, ALK fusion detection was reduced with sensitivities of 87% and 88%, respectively. Idylla had a limited sensitivity of 67% for NTRK fusions, in which only an imbalance assessment was used. Conclusions: UFGFA using NGS and reverse-transcriptase polymerase chain reaction approaches had an equal level of detection of gene fusion but with some technique-specific limitations. Nevertheless, UFGFA detection in routine clinical care is feasible with both systems allowing faster initiation of therapy and a broad degree of screening.

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