AUTHOR=Yang Hong , Li Haojing , Fang Yu , Li Zhijun , Zhu Jianhua , Liu Huan , Lu Chao , Zhang Xiaoyan , Ma Tonghui , Zhang Cuiying 

TITLE=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

JOURNAL=Frontiers in Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.979032

DOI=10.3389/fmed.2022.979032

ISSN=2296-858X

ABSTRACT=<sec><title>Background</title><p>Currently, many targeted drugs are approved for treatment of <italic>ALK</italic> 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 <italic>ALK</italic> inhibitors because of lack of an intact kinase domain.</p></sec><sec><title>Case description</title><p>A novel 5′ NOK fusion form, <italic>ALK-CYP27C1</italic> (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 <italic>EML4-ALK</italic> (E13:A20) fusion variant type I.</p></sec><sec><title>Conclusion</title><p>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 <italic>EML4-ALK</italic> at the RNA level, illustrating the need for RNA testing in 5′ NOK patients.</p></sec>