Background: Approximately 2– 7% of patients with non-small cell lung cancer harbor anaplastic lymphoma kinase (ALK) rearrangement events. Of note, typical ALK actionable rearrangements are sensitive to treatment with tyrosine kinase inhibitors (TKIs). However, different types of ALK fusion influence the clinical outcomes of this therapeutic approach. Approximately 10– 40% of patients with ALK-fusion positive non-small cell lung cancer do not response to ALK-TKI therapy. Therefore, it is important to accurately identify the types of ALK rearrangement for appropriate selection of clinical treatment.
Case Report: Using a DNA-targeted next-generation sequencing technique, we found a novel solute carrier family 8 member A1 (SLC8A1)-ALK fusion type in a patient with lung adenocarcinoma. Further reverse transcriptase-polymerase chain reaction and Sanger sequencing demonstrated the rearrangement as a B-cell CLL/lymphoma 11A (BCL11A)-ALK fusion at the transcriptional level. The patient showed a rapid and strong response to treatment with crizotinib, which lasted for 9 months. The patient also responded well to treatment with alectinib after developed resistance to crizotinib.
Conclusion: A strategy combining DNA-targeted next-generation sequencing with RNA reverse transcriptase-polymerase chain reaction and sequencing, besides fluorescence in situ hybridization and immunohistochemistry, may provide an effective and practical solution for correct identification of partner genes and fusion structures in the diagnosis of ALK rearrangements, particularly for non-canonical expression patterns of ALK fusion events. The combined approach may lead to more benefits for patients.



中文翻译：

---

鉴定一种新的 SLC8A1-ALK 融合和非典型表达对肺腺癌中的 ALK-TKI 有显着反应：病例报告

背景：大约 2-7% 的非小细胞肺癌患者存在间变性淋巴瘤激酶 (ALK) 重排事件。值得注意的是，典型的 ALK 可操作重排对酪氨酸激酶抑制剂 (TKI) 的治疗很敏感。然而，不同类型的 ALK 融合会影响这种治疗方法的临床结果。大约 10-40% 的 ALK 融合阳性非小细胞肺癌患者对 ALK-TKI 治疗没有反应。因此，准确识别 ALK 重排的类型对于临床选择合适的治疗方案非常重要。
案例报告：使用靶向 DNA 的下一代测序技术，我们在肺腺癌患者中发现了一种新型溶质载体家族 8 成员 A1 (SLC8A1)-ALK 融合型。进一步的逆转录酶-聚合酶链反应和 Sanger 测序证明了在转录水平上重排为 B 细胞 CLL/淋巴瘤 11A (BCL11A)-ALK 融合。患者对克唑替尼治疗表现出快速而强烈的反应，持续了 9 个月。在对克唑替尼产生耐药性后，该患者对艾乐替尼的治疗也反应良好。
结论：DNA靶向二代测序与RNA逆转录聚合酶链反应和测序相结合的策略，除了荧光原位杂交和免疫组织化学外，可能为正确识别ALK诊断中的伴侣基因和融合结构提供有效和实用的解决方案重排，特别是对于 ALK 融合事件的非规范表达模式。联合方法可能会为患者带来更多益处。