Oncogenic Function of a KIF5B-MET Fusion Variant in Non-Small Cell Lung Cancer

Neoplasia : an International Journal for Oncology Research
Chien-Hung GowJin-Yuan Shih

Abstract

A kinesin family member 5b (KIF5B)-MET proto-oncogene, receptor tyrosine kinase (MET) rearrangement was reported in patients with lung adenocarcinoma but its oncogenic function was not fully evaluated. We used one-step reverse transcription-polymerase chain reaction for RNA samples to screen for the KIF5B-MET fusion in 206 lung adenocarcinoma and 28 pulmonary sarcomatoid carcinoma patients. Genomic breakpoints of KIF5B-MET were determined by targeted next-generation sequencing. Soft agar colony formation assays, proliferation assays, and a xenograft mouse model were used to investigate its oncogenic activity. In addition, specific MET inhibitors were administered to evaluate their anti-tumor activities. A KIF5B-MET fusion variant in a patient with a mixed-type adenocarcinoma and sarcomatoid tumor was identified, and another case was found in a pulmonary sarcomatoid carcinoma patient. Both cases carried the same chimeric gene, a fusion between exons 1-24 of KIF5B and exons 15-21 of MET. KIF5B-MET-overexpressing cells exhibited significantly increased proliferation and colony-forming ability. Xenograft tumors harboring the fusion gene demonstrated significantly elevated tumor growth. Ectopic expression of the fusion gene stimulat...Continue Reading

Citations

Jun 10, 2020·Nature Reviews. Clinical Oncology·Robin GuoAlexander Drilon
Sep 29, 2019·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Min-Shu HsiehYi-Hsuan Lee
May 5, 2021·Expert Opinion on Therapeutic Targets·Matthew LeeBalazs Halmos
May 19, 2021·World Journal of Clinical Cases·Zhi-Wei WuLi-Jiang Yu

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Methods Mentioned

BETA
xenograft
PCR
biopsy
xenografts

Software Mentioned

picard
IGV2
Excel
- tools
bwa
SPSS
Genome Analysis - TK

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