1. Identification of a novel KIF13A-RET fusion in lung adenocarcinoma by next-generation sequencing
- Author
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Hui Tian, Xuefei Zhang, Ge Sun, Zhibo Miao, Weifeng Wang, Changhong Liu, Xiaowei Dong, Desheng Lv, Ming Yao, Hui Chen, Kai Wang, Mo Li, and Yanlin Li
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,endocrine system ,Cancer Research ,Lung Neoplasms ,Oncogene Proteins, Fusion ,endocrine system diseases ,Cabozantinib ,medicine.medical_treatment ,Kinesins ,Adenocarcinoma of Lung ,Vandetanib ,Bioinformatics ,Translocation, Genetic ,Targeted therapy ,03 medical and health sciences ,Exon ,chemistry.chemical_compound ,0302 clinical medicine ,Asian People ,medicine ,ROS1 ,Humans ,Molecular Targeted Therapy ,Lung cancer ,Protein Kinase Inhibitors ,neoplasms ,Neoplasm Staging ,business.industry ,High-Throughput Nucleotide Sequencing ,Middle Aged ,medicine.disease ,Treatment Outcome ,030104 developmental biology ,Oncology ,Protein kinase domain ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,Adenocarcinoma ,Female ,business ,medicine.drug - Abstract
Objectives RET fusions have been reported in 1–2% of lung adenocarcinomas, and represent an actionable target. Patients whose tumors possess RET fusion are associated with clinical benefit from the treatment with multi-kinase inhibitors such as cabozantinib and vandetanib. Further molecular screening for RET fusions is warranted. Novel KIF13A-RET fusion containing an intact RET kinase domain involving exons 1–18 of KIF13A and exons 12–20 of RET was identified in a lung cancer specimen from an 74-year-old Asian never smoker by next-generation sequencing (NGS) during clinical care. The patient was negative for EGFR, ALK, ROS1 and other putative driver alterations. Fusion analysis is consistent with other described RET fusions and is predicted to result in aberrant constitutive activation caused by dimerization and sensitivity to RET-directed therapies. We describe a novel RET-fusion with molecular characteristics consistent with RET-driven non-small cell lung cancer. Our case expands the spectrum of RET fusion partners and supports broad molecular profiling in non-small cell lung cancer optimizing patient therapeutic options. The new RET fusion has immediate clinical implications for cancer patients.
- Published
- 2018
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