Comprehensive NGS profiling to enable detection of ALK gene rearrangements and MET amplifications in non-small cell lung cancer.

Autor:	Clavé S; Pathology Department, Hospital del Mar, Barcelona, Spain.; Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., Jackson JB; Personal Genome Diagnostics (PGDx/Labcorp), Baltimore, MD, United States., Salido M; Pathology Department, Hospital del Mar, Barcelona, Spain.; Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., Kames J; Personal Genome Diagnostics (PGDx/Labcorp), Baltimore, MD, United States., Gerding KMR; Personal Genome Diagnostics (PGDx/Labcorp), Baltimore, MD, United States., Verner EL; Personal Genome Diagnostics (PGDx/Labcorp), Baltimore, MD, United States., Kong EF; Personal Genome Diagnostics (PGDx/Labcorp), Baltimore, MD, United States., Weingartner E; Personal Genome Diagnostics (PGDx/Labcorp), Baltimore, MD, United States., Gibert J; Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain., Hardy-Werbin M; Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain.; Medical Oncology Department, Hospital del Mar, Barcelona, Spain., Rocha P; Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.; Medical Oncology Department, Hospital del Mar, Barcelona, Spain., Riera X; Pathology Department, Hospital del Mar, Barcelona, Spain.; Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain., Torres E; Pathology Department, Hospital del Mar, Barcelona, Spain., Hernandez J; Personal Genome Diagnostics (PGDx/Labcorp), Baltimore, MD, United States., Cerqueira G; Personal Genome Diagnostics (PGDx/Labcorp), Baltimore, MD, United States., Nichol D; Personal Genome Diagnostics (PGDx/Labcorp), Baltimore, MD, United States., Simmons J; Personal Genome Diagnostics (PGDx/Labcorp), Baltimore, MD, United States., Taus Á; Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain.; Medical Oncology Department, Hospital del Mar, Barcelona, Spain., Pijuan L; Pathology Department, Hospital del Mar, Barcelona, Spain., Bellosillo B; Pathology Department, Hospital del Mar, Barcelona, Spain.; Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., Arriola E; Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.; Medical Oncology Department, Hospital del Mar, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2023 Oct 20; Vol. 13, pp. 1225646. Date of Electronic Publication: 2023 Oct 20 (Print Publication: 2023).
DOI:	10.3389/fonc.2023.1225646
Abstrakt:	Introduction: Next-generation sequencing (NGS) is currently widely used for biomarker studies and molecular profiling to identify concurrent alterations that can lead to the better characterization of a tumor's molecular landscape. However, further evaluation of technical aspects related to the detection of gene rearrangements and copy number alterations is warranted. Methods: There were 12 ALK rearrangement-positive tumor specimens from patients with non-small cell lung cancer (NSCLC) previously detected via fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and an RNA-based NGS assay, and 26 MET high gene copy number (GCN) cases detected by FISH, selected for this retrospective study. All 38 pre-characterized cases were reassessed utilizing the PGDx™ elio™ tissue complete assay, a 505 gene targeted NGS panel, to evaluate concordance with these conventional diagnostic techniques. Results: The detection of ALK rearrangements using the DNA-based NGS assay demonstrated excellent sensitivity with the added benefit of characterizing gene fusion partners and genomic breakpoints. MET copy number alterations were also detected; however, some discordances were observed likely attributed to differences in algorithm, reporting thresholds and gene copy number state. TMB was also assessed by the assay and correlated to the presence of NSCLC driver alterations and was found to be significantly lower in cases with NGS-confirmed canonical driver mutations compared with those without (p=0.0019). Discussion: Overall, this study validates NGS as an accurate approach for detecting structural variants while also highlighting the need for further optimization to enable harmonization across methodologies for amplifications. Competing Interests: Authors JJ, JK, KG, EV, EK, EW, JH, GC, DN, and JS were or are currently employed by Personal Genome Diagnostics (PGDx/Labcorp). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Clavé, Jackson, Salido, Kames, Gerding, Verner, Kong, Weingartner, Gibert, Hardy-Werbin, Rocha, Riera, Torres, Hernandez, Cerqueira, Nichol, Simmons, Taus, Pijuan, Bellosillo and Arriola.)
Databáze:	MEDLINE
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