Shi Junmei, Jia Zhaohui, Zhou Zhiguo, Zhao Liyan, Meng Qingju, Liu Yibing
Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.
Clinical Pharmacology, The First Affiliated Hospital of Xingtai Medical College, Xingtai, People's Republic of China.
Onco Targets Ther. 2023 Feb 17;16:109-114. doi: 10.2147/OTT.S388962. eCollection 2023.
Anaplastic lymphoma kinase (ALK) rearrangements have been reported in 3-7% of non-small-cell lung cancers (NSCLC). ALK has been reported to be fused with a variety of genes in NSCLC. Significant clinical activity was achieved by ALK inhibitors in patients with NSCLC harbouring ALK translocations. We reported on a 48-year-old male Chinese patient with advanced lung adenocarcinoma harboring a novel ALK-LIMS1 who showed no response to crizotinib. The tissue was assayed by immunohistochemistry (IHC) for ALK and showed diffuse expression of ALK. Next-generation sequencing (NGS) was performed on the peripheral blood and tissue. The previous tumor tissue showed diffuse expression of ALK. Tissue and the later peripheral blood revealed a ALK- LIMS1 fusion. The patient failed to benefit from crizotinib (250 mg, twice a day), with a progression-free survival of two months. We identified a new ALK-LIMS1 fusion from an advanced lung adenocarcinoma which was primary resistant to crizotinib. Our case suggested that the coexistence of mutations and the non-dominant clone, as well as the rearrangement of ALK fusion, did not result in expressed ALK kinase domain that might lead to no response to ALK-TKIs.
间变性淋巴瘤激酶(ALK)重排在3%-7%的非小细胞肺癌(NSCLC)中被报道。据报道,在NSCLC中ALK与多种基因融合。ALK抑制剂在携带ALK易位的NSCLC患者中取得了显著的临床活性。我们报道了一名48岁的中国男性晚期肺腺癌患者,其携带一种新的ALK-LIMS1融合基因,对克唑替尼无反应。通过免疫组织化学(IHC)检测组织中的ALK,结果显示ALK呈弥漫性表达。对其外周血和组织进行了二代测序(NGS)。先前的肿瘤组织显示ALK呈弥漫性表达。组织及后来的外周血检测发现ALK-LIMS1融合基因。该患者未从克唑替尼(250mg,每日两次)治疗中获益,无进展生存期为两个月。我们从一例对克唑替尼原发耐药的晚期肺腺癌中鉴定出一种新的ALK-LIMS1融合基因。我们的病例表明,突变与非优势克隆的共存以及ALK融合重排并未导致ALK激酶结构域表达,这可能导致对ALK酪氨酸激酶抑制剂(ALK-TKIs)无反应。