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阿来替尼治疗2例携带不同新型融合基因的非小细胞肺癌患者。

Alectinib treatment for 2 non-small cell lung carcinoma patients carrying different novel fusions.

作者信息

Liang Qingchun, Li Namei, Li Xiaohong

机构信息

Department of Pathology, Second Xiangya Hospital, Central South University, Changsha 410011.

Hunan Clinical Medical Research Center for Cancer Pathogenic Genes Testing and Diagnosis, Changsha 410011, China.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2024 Jul 28;49(7):1164-1172. doi: 10.11817/j.issn.1672-7347.2024.230503.

Abstract

The genomic fusions of the anaplastic lymphoma kinase () gene have been widely recognized as effective therapeutic targets for non-small cell lung carcinoma (NSCLC). The Second Xiangya Hospital of Central South University has treated 2 NSCLC patients with 2 distinct novel gene fusions. Case 1 was a 55-year-old male with a solid nodule located in the right hilar lobe on enhanced CT scan. Case 2 was a 47-year-old female with enhanced CT showing involvement of the left upper lobe of lung. Histopathological examination of tumor tissues confirmed lung adenocarcinoma in both cases. Immunohistochemical (IHC) staining demonstrated positivity for thyroid transcription factor-1 (TTF-1) and ALK-D5F3 in tumor cells, while negativity for P40. The next-generation sequencing (NGS) tests identified a - (Exon22:Exon20) fusion variant in case 1 and a - (Exon3:Exon19) fusion variant in case 2. The - fusion was further confirmed by amplification refractory mutation system (ARMS)-PCR at the mRNA level. Both patients were treated with oral alectinib at a dosage of 600 mg twice daily. The tumors in both patients were significantly decreased after alectinib treatment, achieving partial response. At the time of submission, there was an absence of disease progression and the progression-free survival (PFS) had surpassed 1 year. It offered compelling evidences that the individuals with NSCLC and harboring either a - (Exon22:Exon20) fusion or a - (Exon3:Exon19) fusion, experience favorable therapeutic outcomes through the administration of alectinib. This study expands the known fusion variants database and supports the precision treatment of NSCLC using tyrosine kinase inhibitors (TKIs).

摘要

间变性淋巴瘤激酶(ALK)基因的基因组融合已被广泛认为是非小细胞肺癌(NSCLC)有效的治疗靶点。中南大学湘雅二医院治疗了2例具有2种不同新型ALK基因融合的NSCLC患者。病例1是一名55岁男性,增强CT扫描显示右肺门叶有实性结节。病例2是一名47岁女性,增强CT显示左肺上叶受累。肿瘤组织的组织病理学检查证实两例均为肺腺癌。免疫组织化学(IHC)染色显示肿瘤细胞中甲状腺转录因子-1(TTF-1)和ALK-D5F3呈阳性,而P40呈阴性。二代测序(NGS)检测在病例1中鉴定出一种EML4-ALK(外显子22:外显子20)融合变异体,在病例2中鉴定出一种KIF5B-ALK(外显子3:外显子19)融合变异体。通过扩增阻滞突变系统(ARMS)-PCR在mRNA水平进一步证实了EML4-ALK融合。两名患者均接受口服阿来替尼治疗,剂量为每日两次,每次600 mg。阿来替尼治疗后,两名患者的肿瘤均显著缩小,达到部分缓解。在提交本文时,无疾病进展,无进展生存期(PFS)已超过1年。这提供了令人信服的证据,即患有NSCLC且携带EML4-ALK(外显子22:外显子20)融合或KIF5B-ALK(外显子3:外显子19)融合的个体,通过服用阿来替尼可获得良好的治疗效果。本研究扩展了已知的ALK融合变异体数据库,并支持使用ALK酪氨酸激酶抑制剂(TKIs)对NSCLC进行精准治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7072/11495982/c93a2d526df1/ZhongNanDaXueXueBaoYiXueBan-49-7-1164-g001.jpg

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