Robust Performance of the Novel Research-Use-Only Idylla GeneFusion Assay Using a Diverse Set of Pathological Samples with a Proposed 1-Day Workflow for Advanced NSCLC Evaluation

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2023 Jan 8

PMID 36612287

Authors

Alvaro Leone

Lucia Anna Muscarella

Paolo Graziano

Andrea Tornese

Lucia Rosalba Grillo

Angela Di Lorenzo

Monica Bronzini

Stefania Scarpino

Angelo Sparaneo

Giulio Rossi

Affiliations

Soon will be listed here.

Abstract

A range of different techniques are available for predictive biomarker testing for non-small-cell lung cancer (NSCLC) clinical management. International guidelines suggest next-generation sequencing (NGS) as the preferred procedure, but other reverse transcriptase-polymerase chain reaction (RT-PCR)-based methods are rapidly evolving. In this study, we evaluated the reliability and accuracy of the Idylla GeneFusion assay, a rapid and fully automated platform able to simultaneously detect , , and and ex14 skipping mutations and compared its performance with routine reference methods. The cohort included thirty-seven NSCLCs plus two parotid gland carcinomas, previously characterized for the above alterations through either IHC, FISH, RT-PCR or NGS. In 36 of 39 cases, the Idylla GeneFusion assay and the reference methods were concordant (overall agreement: 92.3%). Tumor sections stored at room temperature for up to 60 days and 17 cases older than 2 years were successfully characterized. Our results suggest that the Idylla GeneFusion assay is a reliable tool to define gene fusion status and may be a valuable stand-alone diagnostic test when time efficiency is needed or NGS is not feasible.

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References

Lee S, Lee B, Hong M, Song J, Jung K, Lira M . Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma. Mod Pathol. 2014; 28(4):468-79. DOI: 10.1038/modpathol.2014.107. View

Williams H, Walsh K, Diamond A, Oniscu A, Deans Z . Validation of the Oncomine focus panel for next-generation sequencing of clinical tumour samples. Virchows Arch. 2018; 473(4):489-503. PMC: 6182325. DOI: 10.1007/s00428-018-2411-4. View

Fujii T, Uchiyama T, Matsuoka M, Myojin T, Sugimoto S, Nitta Y . Evaluation of DNA and RNA quality from archival formalin-fixed paraffin-embedded tissue for next-generation sequencing - Retrospective study in Japanese single institution. Pathol Int. 2020; 70(9):602-611. DOI: 10.1111/pin.12969. View

Nozaki Y, Yamamoto H, Iwasaki T, Sato M, Jiromaru R, Hongo T . Clinicopathological features and immunohistochemical utility of NTRK-, ALK-, and ROS1-rearranged papillary thyroid carcinomas and anaplastic thyroid carcinomas. Hum Pathol. 2020; 106:82-92. DOI: 10.1016/j.humpath.2020.09.004. View

Liu F, Wei Y, Zhang H, Jiang J, Zhang P, Chu Q . NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance. Front Oncol. 2022; 12:864666. PMC: 8968138. DOI: 10.3389/fonc.2022.864666. View

De Marchi F, Haley L, Fryer H, Ibrahim J, Beierl K, Zheng G . Clinical Validation of Coexisting Activating Mutations Within EGFR, Mitogen-Activated Protein Kinase, and Phosphatidylinositol 3-Kinase Pathways in Lung Cancers. Arch Pathol Lab Med. 2018; 143(2):174-182. DOI: 10.5858/arpa.2017-0495-OA. View

Ambrosini-Spaltro A, Farnedi A, Calistri D, Rengucci C, Prisinzano G, Chiadini E . The role of next-generation sequencing in detecting gene fusions with known and unknown partners: a single-center experience with methodologies' integration. Hum Pathol. 2022; 123:20-30. DOI: 10.1016/j.humpath.2022.02.005. View

Kris M, Johnson B, Berry L, Kwiatkowski D, Iafrate A, Wistuba I . Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014; 311(19):1998-2006. PMC: 4163053. DOI: 10.1001/jama.2014.3741. View

Lira M, Choi Y, Lim S, Deng S, Huang D, Ozeck M . A single-tube multiplexed assay for detecting ALK, ROS1, and RET fusions in lung cancer. J Mol Diagn. 2014; 16(2):229-43. DOI: 10.1016/j.jmoldx.2013.11.007. View

10.

Aguado C, Gimenez-Capitan A, Roman R, Rodriguez S, Jordana-Ariza N, Aguilar A . RNA-Based Multiplexing Assay for Routine Testing of Fusion and Splicing Variants in Cytological Samples of NSCLC Patients. Diagnostics (Basel). 2020; 11(1). PMC: 7824402. DOI: 10.3390/diagnostics11010015. View

11.

Depoilly T, Garinet S, van Kempen L, Schuuring E, Clave S, Bellosillo B . Multicenter Evaluation of the Idylla GeneFusion in Non-Small-Cell Lung Cancer. J Mol Diagn. 2022; 24(9):1021-1030. DOI: 10.1016/j.jmoldx.2022.05.004. View

12.

Howlader N, Forjaz G, Mooradian M, Meza R, Kong C, Cronin K . The Effect of Advances in Lung-Cancer Treatment on Population Mortality. N Engl J Med. 2020; 383(7):640-649. PMC: 8577315. DOI: 10.1056/NEJMoa1916623. View

13.

Teishikata T, Shiraishi K, Shinno Y, Kobayashi Y, Kashima J, Ishiyama T . An Alert to Possible False Positives With a Commercial Assay for MET Exon 14 Skipping. J Thorac Oncol. 2021; 16(12):2133-2138. DOI: 10.1016/j.jtho.2021.07.028. View

14.

Solomon J, Hechtman J . Detection of Fusions: Merits and Limitations of Current Diagnostic Platforms. Cancer Res. 2019; 79(13):3163-3168. PMC: 6606326. DOI: 10.1158/0008-5472.CAN-19-0372. View

15.

Pan Y, Zhang Y, Li Y, Hu H, Wang L, Li H . ALK, ROS1 and RET fusions in 1139 lung adenocarcinomas: a comprehensive study of common and fusion pattern-specific clinicopathologic, histologic and cytologic features. Lung Cancer. 2014; 84(2):121-6. DOI: 10.1016/j.lungcan.2014.02.007. View

16.

Sorber L, Van Dorst B, Bellon E, Zwaenepoel K, Lambin S, De Winne K . NTRK Gene Fusion Detection in a Pan-Cancer Setting Using the Idylla GeneFusion Assay. J Mol Diagn. 2022; 24(7):750-759. DOI: 10.1016/j.jmoldx.2022.03.014. View

17.

Park G, Kim T, Lee H, Lim J, Won J, Min H . Standard immunohistochemistry efficiently screens for anaplastic lymphoma kinase rearrangements in differentiated thyroid cancer. Endocr Relat Cancer. 2014; 22(1):55-63. DOI: 10.1530/ERC-14-0467. View

18.

Yang S, Aypar U, Rosen E, Mata D, Benayed R, Mullaney K . A Performance Comparison of Commonly Used Assays to Detect RET Fusions. Clin Cancer Res. 2020; 27(5):1316-1328. PMC: 8285056. DOI: 10.1158/1078-0432.CCR-20-3208. View

19.

Chu Y, Barbee J, Yang S, Chang J, Liang P, Mullaney K . Clinical Utility and Performance of an Ultrarapid Multiplex RNA-Based Assay for Detection of ALK, ROS1, RET, and NTRK1/2/3 Rearrangements and MET Exon 14 Skipping Alterations. J Mol Diagn. 2022; 24(6):642-654. PMC: 9227998. DOI: 10.1016/j.jmoldx.2022.03.006. View

20.

Evangelista A, Zanon M, Carloni A, Paula F, Morini M, Ferreira-Neto M . Detection of ALK fusion transcripts in FFPE lung cancer samples by NanoString technology. BMC Pulm Med. 2017; 17(1):86. PMC: 5446704. DOI: 10.1186/s12890-017-0428-0. View