Department of Medical Examination, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, PR China.
Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, PR China.
Cancer Genet. 2023 Nov;278-279:18-23. doi: 10.1016/j.cancergen.2023.08.003. Epub 2023 Aug 9.
Non-small-cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) fusion showed promising responses to ALK tyrosine kinase inhibitors (TKIs). In this study, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), next generation sequencing (NGS) and Sanger sequencing were performed to identify the presence of ALK fusion, to investigate whether the patient may benefit from TKI therapy. Postoperative pathological analysis indicated invasive adenocarcinoma with mainly mucinous type and partial micropapillary type in left lower lung. Minimally invasive adenocarcinoma was seen in left upper lung, with mainly acinar type. NGS detected a novel RSRC1-ALK (R6: A20) fusion in left lower lobe sample, which was presented as the fusion of exon 6 of RSRC1 and exon 20 of ALK gene. Sanger sequencing validated the fusion. Break rearrangement signal of ALK gene was detected in 80% of tumor cells. Immunohistochemistry showed ALK positive expression in lung. For the treatment, the patient received ensartinib hydrochloride with a dose of 225 mg per day. He was in a state of progression-free survival for at least 24 months in follow-up with no complications. NGS can be used for exploring treatment options for NSCLC patients with ALK fusion.
非小细胞肺癌（NSCLC）患者存在间变性淋巴瘤激酶（ALK）融合时，对 ALK 酪氨酸激酶抑制剂（TKI）有显著的反应。在这项研究中，采用荧光原位杂交（FISH）、免疫组织化学（IHC）、下一代测序（NGS）和 Sanger 测序来鉴定 ALK 融合的存在，以研究患者是否可能从 TKI 治疗中获益。术后病理分析显示左肺下叶为主要黏液型和部分微乳头型的浸润性腺癌。左上肺为微浸润性腺癌，以腺泡型为主。NGS 在左肺下叶样本中检测到一种新的 RSRC1-ALK（R6:A20）融合，表现为 RSRC1 外显子 6 和 ALK 基因外显子 20 的融合。Sanger 测序验证了融合。ALK 基因的断裂重排信号在 80%的肿瘤细胞中被检测到。免疫组织化学显示肺组织中 ALK 阳性表达。治疗上，患者接受盐酸恩沙替尼治疗，剂量为每天 225mg。在随访中，他至少 24 个月无进展生存，无并发症。NGS 可用于探索 ALK 融合的 NSCLC 患者的治疗选择。
