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

Frontiers in Oncology

Oncology

Joan Gibert¹  Edurne Arriola²  Pedro Rocha²  Max Hardy-Werbin³  Álvaro Taus³  Erica Torres⁴  Lara Pijuan⁴  Xènia Riera⁵  Sergi Clavé⁶  Beatriz Bellosillo⁶  Marta Salido⁶  Eric F. Kong⁷  John Simmons⁷  Gustavo Cerqueira⁷  Ellen L. Verner⁷  James Hernandez⁷  Jennifer B. Jackson⁷  Kelly M. R. Gerding⁷  Elizabeth Weingartner⁷  Donna Nichol⁷  Jacob Kames⁷ 

[1] Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain;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;Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain;Medical Oncology Department, Hospital del Mar, Barcelona, Spain;Pathology Department, Hospital del Mar, Barcelona, Spain;Pathology Department, Hospital del Mar, Barcelona, Spain;Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain;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;Personal Genome Diagnostics (PGDx/Labcorp), Baltimore, MD, United States;

关键词: next generation sequencing (NGS);    non-small cell lung cancer (NSCLC);    MET;    ALK;    in situ;    biomarkers;    molecular testing;   

DOI  :  10.3389/fonc.2023.1225646

 received in 2023-05-19, accepted in 2023-08-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionNext-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.MethodsThere 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.ResultsThe 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).DiscussionOverall, 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.

【 授权许可】

Unknown   
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