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Updated: May 26, 2026
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome
Young Seok Ju1, Won-Chul Lee, Jong-Yeon Shin
1Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea.
Abstract:
The identification of the molecular events that drive cancer transformation is essential to the development of targeted agents that improve the clinical outcome of lung cancer. Many studies have reported genomic driver mutations in non-small-cell lung cancers (NSCLCs) over the past decade; however, the molecular pathogenesis of >40% of NSCLCs is still unknown. To identify new molecular targets in NSCLCs, we performed the combined analysis of massively parallel whole-genome and transcriptome sequencing for cancer and paired normal tissue of a 33-yr-old lung adenocarcinoma patient, who is a never-smoker and has no familial cancer history. The cancer showed no known driver mutation in EGFR or KRAS and no EML4-ALK fusion. Here we report a novel fusion gene between KIF5B and the RET proto-oncogene caused by a pericentric inversion of 10p11.22-q11.21. This fusion gene overexpresses chimeric RET receptor tyrosine kinase, which could spontaneously induce cellular transformation. We identified the KIF5B-RET fusion in two more cases out of 20 primary lung adenocarcinomas in the replication study. Our data demonstrate that a subset of NSCLCs could be caused by a fusion of KIF5B and RET, and suggest the chimeric oncogene as a promising molecular target for the personalized diagnosis and treatment of lung cancer.
Insights
Researchers discovered a novel KIF5B-RET fusion gene in lung adenocarcinoma. This fusion drives cancer development and presents a new target for personalized lung cancer treatments.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Understanding molecular drivers of lung cancer is crucial for developing targeted therapies.
- Over 40% of non-small-cell lung cancers (NSCLCs) lack identified molecular pathogenesis.
- Previous research identified common mutations like EGFR, KRAS, and EML4-ALK fusions.
Observation:
- Whole-genome and transcriptome sequencing were performed on a never-smoker lung adenocarcinoma patient with no family cancer history.
- The patient's tumor lacked known driver mutations (EGFR, KRAS) and EML4-ALK fusion.
- A novel fusion gene involving KIF5B and the RET proto-oncogene was identified due to a pericentric inversion.
Findings:
- The KIF5B-RET fusion gene leads to overexpression of a chimeric RET receptor tyrosine kinase.
- This chimeric protein can induce spontaneous cellular transformation.
- The KIF5B-RET fusion was detected in 2 out of 20 additional primary lung adenocarcinoma cases.
Implications:
- A subset of NSCLCs are driven by the KIF5B-RET fusion oncogene.
- This fusion represents a potential molecular target for personalized lung cancer diagnosis and therapy.
- Further research into KIF5B-RET may lead to novel therapeutic strategies for lung adenocarcinoma.
