J Pathol Transl Med.  2018 May;52(3):148-156. 10.4132/jptm.2018.03.12.

Molecular Screening of Small Biopsy Samples Using Next-Generation Sequencing in Korean Patients with Advanced Non-small Cell Lung Cancer: Korean Lung Cancer Consortium (KLCC-13-01)

Affiliations
  • 1Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 2Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. silk.ahn@samsung.com
  • 3CHA Bundang Medical Center, CHA University, Seongnam, Korea.
  • 4Division of Medical Oncology, Yonsei Cancer Center, Seoul, Korea.
  • 5Division of Hematology and Medical Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
  • 6Division of Oncology, Department of Hematology and Oncology, Ulsan University Hospital, Ulsan, Korea.
  • 7Division of Medical Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea.
  • 8Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 9Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. kj2011.lee@samsung.com

Abstract

BACKGROUND
Non-small cell lung cancer (NSCLC) is a common type of cancer with poor prognosis. As individual cancers exhibit unique mutation patterns, identifying and characterizing gene mutations in NSCLC might help predict patient outcomes and guide treatment. The aim of this study was to evaluate the clinical adequacy of molecular testing using next-generation sequencing (NGS) for small biopsy samples and characterize the mutational landscape of Korean patients with advanced NSCLC.
METHODS
DNA was extracted from small biopsy samples of 162 patients with advanced NSCLC. Targeted NGS of genomic alterations was conducted using Ion AmpliSeq Cancer Hotspot Panel v2.
RESULTS
The median age of patients was 64 years (range, 32 to 83 years) and the majority had stage IV NSCLC at the time of cancer diagnosis (90%). Among the 162 patients, 161 patients (99.4%) had novel or hotspot mutations (range, 1 to 21 mutated genes). Mutations were found in 41 genes. Three of the most frequently mutated genes were TP53 (151, 93.2%), KDR (104, 64.2%), and epidermal growth factor receptor (EGFR; 69, 42.6%). We also observed coexistence of EGFR and other oncogene (such as KRAS, PIC3CA, PTEN, and STK11) mutations. Given that 69.6% (48/69) of EGFR mutant patients were treated with EGFR tyrosine kinase inhibitors, EGFR mutant status had higher prognostic ability in this study.
CONCLUSIONS
These results suggest that targeted NGS using small biopsy samples is feasible and allows for the detection of both common and rare mutations in NSCLC.

Keyword

Carcinoma, non-small cell lung; Targeted next-generation sequencing; Small biopsy; Receptor, epidermal growth factor

MeSH Terms

Biopsy*
Carcinoma, Non-Small-Cell Lung*
Diagnosis
DNA
Humans
Lung Neoplasms*
Lung*
Mass Screening*
Oncogenes
Prognosis
Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor
DNA
Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor

Figure

  • Fig. 1. Heatmap of mutations found in 162 non-small cell lung cancer samples. In the upper panel, the first row indicates sex, the second row smoking status, and the third row histology. A histogram shows the percentage of mutations in each gene (let). The horizontal axis presents the complete dataset of patients and the vertical axis illustrates mutated genes (right).

  • Fig. 2. Impact of epidermal growth factor receptor (EGFR) mutational status on survival. (A) Progression-free survival of patients with EGFR mutant (MT) compared with EGFR wild-type (WT) patients. (B) Overall survival of all patients according to EGFR status. p-values were obtained using the log-rank test.

  • Fig. 3. Impact of different types of epidermal growth factor receptor (EGFR) mutations on survival. Progression-free survival (A) and overall survival (B) of patients with different types of EGFR mutations compared with EGFR wild type (WT) patients. p-values were obtained using the log-rank (Mantel-Cox) test.


Cited by  2 articles

Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group
Sunhee Chang, Hyo Sup Shim, Tae Jung Kim, Yoon-La Choi, Wan Seop Kim, Dong Hoon Shin, Lucia Kim, Heae Surng Park, Geon Kook Lee, Chang Hun Lee
J Pathol Transl Med. 2021;55(3):181-191.    doi: 10.4132/jptm.2021.03.23.

Landscape of EGFR mutations in lung adenocarcinoma: a single institute experience with comparison of PANAMutyper testing and targeted next-generation sequencing
Jeonghyo Lee, Yeon Bi Han, Hyun Jung Kwon, Song Kook Lee, Hyojin Kim, Jin-Haeng Chung
J Pathol Transl Med. 2022;56(5):249-259.    doi: 10.4132/jptm.2022.06.11.


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