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Table_2_A non-functional 5′ ALK fusion validated at the RNA level as a classical EML4-ALK that responds well to the novel ALK inhibitor ensartinib: A .DOCX (21.82 kB)
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Table_2_A non-functional 5′ ALK fusion validated at the RNA level as a classical EML4-ALK that responds well to the novel ALK inhibitor ensartinib: A case report.DOCX

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posted on 2022-10-06, 04:29 authored by Hong Yang, Haojing Li, Yu Fang, Zhijun Li, Jianhua Zhu, Huan Liu, Chao Lu, Xiaoyan Zhang, Tonghui Ma, Cuiying Zhang
Background

Currently, many targeted drugs are approved for treatment of ALK fusion non-small cell lung cancer. However, it has been previously assumed that patients with 5′ non-oncogenic kinase (5′ NOK) fusion detected by DNA next-generation sequencing (NGS) would not benefit from ALK inhibitors because of lack of an intact kinase domain.

Case description

A novel 5′ NOK fusion form, ALK-CYP27C1 (A19:C5), was detected by DNA NGS in surgical tissue specimens of a patient with recurrent lung adenosquamous carcinoma. The patient achieved 29 months of progression-free survival with ensartinib treatment. The results of RNA NGS from the same operative tissue identified EML4-ALK (E13:A20) fusion variant type I.

Conclusion

This is the first case to provide real-world evidence of effective treatment of a patient with the 5′ NOK fusion form at the DNA level but functional EML4-ALK at the RNA level, illustrating the need for RNA testing in 5′ NOK patients.

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