Related Experiment Video
Updated: Jun 15, 2026
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene
Tsuyoshi Takahashi1, Makoto Sonobe, Masashi Kobayashi
1Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Background:
A fusion gene between echinoderm microtubule-associated protein-like 4 (EML4) and the anaplastic lymphoma kinase (ALK) has recently been identified in nonsmall-cell lung cancers (NSCLCs). We screened for EML4-ALK fusion genes and examined the clinicopathological and genetic characteristics of fusion-harboring NSCLC tumors.
Methods:
We examined 313 NSCLC samples from patients who underwent resection at our hospital between May 2001 and July 2005. We screened for the fusion genes using reverse-transcription polymerase chain reaction (RT-PCR) assay and confirmed the results with direct sequencing. We also examined mutations in the epidermal growth factor receptor (EGFR), KRAS, and ERBB2 genes.
Results:
Five EML4-ALK fusion genes were detected (four from 111 female samples and one from 202 male samples; 1.6% overall). All five genes were found in adenocarcinomas and accounted for 2.4% of the 211 adenocarcinoma samples. One EML4-ALK fusion was variant 1, and two were variant 3. In addition, we also found two new fusion variants. Patients with fusion-positive tumors were nonsmokers or light smokers. Among the 211 adenocarcinomas, mutations in EGFR, KRAS, and ERBB2 were detected in 105, 29, and 7 tumors, respectively. Interestingly, all of the fusion-positive NSCLCs had no mutations within these genes.
Conclusions:
EML4-ALK fusion genes were observed predominantly in adenocarcinomas, in female or nonsmoking populations. Additionally, the EML4-ALK fusions were mutually exclusive with mutations in the EGFR, KRAS, and ERBB2 genes.
Insights
Echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusions were found in 1.6% of non-small cell lung cancer (NSCLC) patients. These fusions occurred in adenocarcinomas and were mutually exclusive with EGFR, KRAS, and ERBB2 mutations.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) can harbor a fusion gene between echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK).
- Understanding the prevalence and characteristics of EML4-ALK fusion is crucial for targeted therapy development in NSCLC.
Purpose of the Study:
- To screen for EML4-ALK fusion genes in NSCLC tumors.
- To investigate the clinicopathological and genetic features of NSCLC tumors harboring EML4-ALK fusions.
Main Methods:
- Reverse-transcription polymerase chain reaction (RT-PCR) was used to screen 313 NSCLC samples for EML4-ALK fusion genes.
- Direct sequencing confirmed fusion gene results. Mutations in epidermal growth factor receptor (EGFR), KRAS, and ERBB2 genes were also analyzed.
Main Results:
- EML4-ALK fusions were detected in 1.6% of NSCLC patients (5 out of 313), predominantly in adenocarcinomas (2.4% of 211).
- Fusion-positive NSCLC patients were typically non-smokers or light smokers and predominantly female.
- All EML4-ALK fusion-positive tumors lacked mutations in EGFR, KRAS, and ERBB2.
Conclusions:
- EML4-ALK fusion genes are more common in adenocarcinomas, particularly in female and non-smoking NSCLC patients.
- The presence of EML4-ALK fusions is mutually exclusive with mutations in EGFR, KRAS, and ERBB2, suggesting distinct molecular subtypes of NSCLC.
More Related Videos
10:35A Blood-based Test for the Detection of ROS1 and RET Fusion Transcripts from Circulating Ribonucleic Acid Using Digital Polymerase Chain Reaction
Published on: April 5, 2018
07:59Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023