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)

• Ku BM
• Heo MH
• Kim JH
• Cho BC
• Cho EK
• Min YJ
• Lee KH
• Sun JM
• Lee SH
• Ahn JS
• Park K
• Kim TJ
• Lee HY
• Kim H
• Lee KJ
• Ahn MJ

• KMID: 2412926
• DOI: http://doi.org/10.4132/jptm.2018.03.12

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.

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