Zhu Xingyu, He Yuqi, Wang Yin, Lei Yan, Su Xiaoxing, Liu Yifan, Wu Shuangxiu, He Zhengfu
Department of Thoracic Surgery, Sir Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People's Republic of China.
Monash School of Medicine, Monash University, Clayton, VIC, 3800, Australia.
Onco Targets Ther. 2021 Sep 27;14:4915-4920. doi: 10.2147/OTT.S319845. eCollection 2021.
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.
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.
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.
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，典型的可靶向ALK的重排对酪氨酸激酶抑制剂（TKIs）治疗敏感。然而，不同类型的ALK融合会影响这种治疗方法的临床结果。约10%-40%的ALK融合阳性非小细胞肺癌患者对ALK-TKI治疗无反应。因此，准确识别ALK重排类型对于临床治疗的合理选择至关重要。
我们使用靶向DNA的二代测序技术，在一名肺腺癌患者中发现了一种新的溶质载体家族8成员A1（SLC8A1）-ALK融合类型。进一步的逆转录聚合酶链反应和桑格测序显示，在转录水平上该重排为B细胞CLL/淋巴瘤11A（BCL11A）-ALK融合。该患者对克唑替尼治疗表现出快速且强烈的反应，持续了9个月。在对克唑替尼产生耐药性后，该患者对阿来替尼治疗也有良好反应。
除荧光原位杂交和免疫组化外，将靶向DNA的二代测序与RNA逆转录聚合酶链反应及测序相结合的策略，可能为ALK重排诊断中正确识别伙伴基因和融合结构提供有效且实用的解决方案，特别是对于ALK融合事件的非典型表达模式。这种联合方法可能会给患者带来更多益处。
