Cancer Res Treat.  2020 Apr;52(2):543-551. 10.4143/crt.2019.305.

Detection of Targetable Genetic Alterations in Korean Lung CancerPatients: A Comparison Study of Single-Gene Assays andTargeted Next-Generation Sequencing

  • 1Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea


Epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) are ‘must-test’ biomarkers in the molecular diagnostics of advanced- stage lung cancer patients. Although single-gene assays are currently considered the gold standard for these genes, next-generation sequencing (NGS) tests are being introduced to clinical practices. We compared the results of current diagnostics and aimed to suggest timely effective guidance for their clinical use.
Materials and Methods
Patients with lung cancer who received both conventional single-gene assays and subsequent targeted NGS testing were enrolled, and the results of their tests were compared.
A total of 241 patients were enrolled, and the EGFR real-time polymerase chain reaction, ALK fluorescence in situ hybridization (FISH), and ROS1 FISH assays exhibited 92.9%, 99.6%, and 99.5% concordance with the NGS tests, respectively. The discordant cases were mostly false-negatives of the single-gene assays, probably due to technical limitation. Of 158 cases previously designated as wild-type, EGFR, ALK, and ROS1 alterations were identified in 10.1%, 1.9%, and 1.3%, respectively, and other targetable alterations were identified in 36.1% of the cases. Of patients with additionally identified actionable alterations, 32.6% (31/95) received matched therapy with a clinical benefit of 48.4% (15/31).
Even though the conventional and NGS methods were concordant in the majority of cases, NGS testing still revealed a considerable number of additional EGFR, ALK, and ROS1 alterations, as well as other targetable alterations, in Korean advanced-stage lung cancer patients. Given the high frequency of EGFR and other targetable mutations identified in the present study, NGS testing is highly recommended in the diagnosis of Korean lung cancer patients.


Lung neoplasms; Molecular diagnostics; Next-generation sequencing; Epidermal growth factor receptor; Anaplastic lymphoma kinase; ROS proto-oncogene 1 (ROS1)


  • Fig. 1. Next-generation sequencing (NGS)–detected alterations identified in 158 cases previously designated as wild-type. (A) Distribution of potentially actionable genetic alterations. (B) Distribution of genetic alterations. Variant classification was based on recommendations from the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists [8]. EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma kinase; ROS1, ROS proto-oncogene 1; IDH1, isocitrate dehydrogenase 1; FGFR1, fibroblast growth factor receptor 1; PIK3CA, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha; NF1, neurofibromin 1.

  • Fig. 2. Proposed algorithm for the molecular diagnostics of advanced-stage lung cancer patients. In terms of turnaround time and frequency of major genetic alterations, single-gene testing can be performed first. When results of single-gene assays are negative or clinically indicated, next-generation sequencing (NGS) testing should be performed. The NGS testing can be performed first, so this is also shown in this figure. EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma kinase; ROS1, ROS proto-oncogene 1; IHC, immunohistochemistry; FISH, fluorescence in situ hybridization.

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