Gu Xiaodong, Wang Wenxian, Wu Wei, Zhang Yiping, Shao Lan, Santarpia Mariacarmela, Christopoulos Petros, Myall Nathaniel J, Shi Zhiyong, Lou Guangyuan
The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, China.
Department of Thoracic Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.
Transl Lung Cancer Res. 2022 May;11(5):902-909. doi: 10.21037/tlcr-22-288.
Anaplastic lymphoma kinase (ALK) fusion is an important oncogenic driver in non-small cell lung cancer (NSCLC). Reports on the intergenic region (IGR) as an ALK fusion partner are rare. Here, we report the case of a patient with advanced NSCLC harboring a human immunodeficiency virus type I enhancer binding protein 1 (HIVEP1)-ALK fusion that responded effectively to alectinib.
A 60-year-old non-smoking male was referred with a 3-month history of productive cough secondary to lung adenocarcinoma metastatic to mediastinal lymph nodes, brain, liver, and bone (T2N3M1c, stage IVB). Next-generation sequencing identified an IGR (upstream HIVEP1-) ALK fusion, and immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) results were consistent with an ALK-positive tumor. The patient was subsequently started on alectinib, with no obvious adverse reaction. After 1 month of therapy, the patient achieved significantly remission of the clinical symptoms and had led to an ongoing partial response (PR) lasting >33 months.
Our experience highlights the efficacy of alectinib in a patient with HIVEP1-ALK fusion positive NSCLC with multiple metastases including brain disease, and the need for multiple genetic testing methods to verify the oncogenicity of ALK fusions prior to treatment. It could provide useful guidance for the treatment of similar cases in the future.
间变性淋巴瘤激酶（ALK）融合是非小细胞肺癌（NSCLC）中一种重要的致癌驱动因素。关于基因间区域（IGR）作为ALK融合伴侣的报道很少。在此，我们报告一例晚期NSCLC患者，其携带I型人类免疫缺陷病毒增强子结合蛋白1（HIVEP1）-ALK融合基因，对阿来替尼有效。
一名60岁不吸烟男性因肺腺癌转移至纵隔淋巴结、脑、肝和骨（T2N3M1c，IVB期）导致的3个月咳痰病史前来就诊。二代测序鉴定出一种IGR（上游HIVEP1-）-ALK融合基因，免疫组织化学（IHC）和荧光原位杂交（FISH）结果与ALK阳性肿瘤一致。该患者随后开始接受阿来替尼治疗，无明显不良反应。治疗1个月后，患者临床症状显著缓解，持续部分缓解（PR）超过33个月。
我们的经验强调了阿来替尼对伴有包括脑部疾病在内的多处转移的HIVEP1-ALK融合阳性NSCLC患者的疗效，以及在治疗前需要多种基因检测方法来验证ALK融合的致癌性。这可为未来类似病例的治疗提供有用指导。
