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

BackgroundCurrently, 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 descriptionA 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.
ConclusionThis 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.

背景 目前，多款靶向药物已获批用于间变性淋巴瘤激酶（ALK，Anaplastic Lymphoma Kinase）融合阳性非小细胞肺癌的治疗。但既往观点认为，通过DNA二代测序（NGS，Next-Generation Sequencing）检出携带5′非致癌激酶（5′ NOK，5′ non-oncogenic kinase）融合的患者，因缺乏完整激酶结构域，无法从ALK抑制剂治疗中获益。
病例描述 本研究采用DNA二代测序（NGS），在1例复发性肺腺鳞癌患者的手术组织标本中检出一种新型5′非致癌激酶融合变异型：ALK-CYP27C1（A19:C5）。该患者接受恩沙替尼（ensartinib）治疗后，获得了29个月的无进展生存期。对同一手术组织的RNA二代测序结果显示，存在EML4-ALK（E13:A20）I型融合变异。
结论 本研究首次提供真实世界证据，证实携带DNA层面5′非致癌激酶融合、但RNA层面存在功能性EML4-ALK融合的患者，可从ALK抑制剂治疗中获益，提示对5′非致癌激酶融合患者需开展RNA检测。