PDF(Pubmed)
Abstract：
Approximately 3-5% of non-small cell lung cancers (NSCLC) harbor ALK fusion genes and may be responsive to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors. There are only a few reports on cell lines with EML4-ALK variant 3 (v3) and tumoroids that can be subject to long-term culture (> 3 months). In this study, we established tumoroids (PDT-LUAD#119) from a patient with lung cancer harboring EML4-ALK that could be cultured for 12 months. Whole-exome sequencing and RNA sequencing analyses revealed TP53 mutations and an EML4-ALK v3 mutation. PDT-LUAD#119 lung tumoroids were sensitive to the ALK tyrosine kinase inhibitors (ALK TKIs) crizotinib, alectinib, entrectinib, and lorlatinib, similar to NCI-H3122 cells harboring EML4-ALK variant 1 (v1). Unexpectedly, clear squamous cell carcinoma and solid adenocarcinoma were observed in xenografts from PDT-LUAD#119 lung tumoroids, indicating adenosquamous carcinoma. Immunostaining revealed that the squamous cell carcinoma was ALK positive, suggesting a squamous transformation of the adenocarcinoma. Besides providing a novel cancer model to support basic research on ALK-positive lung cancer, PDT-LUAD#119 lung tumoroids will help elucidate the pathogenesis of adenosquamous carcinoma.
摘要：
大约3-5%的非小细胞肺癌(NSCLC)含有ALK融合基因,并且可能对间变性淋巴瘤激酶(ALK)酪氨酸激酶抑制剂有反应。关于具有EML4-ALK变体3(v3)和可经受长期培养(>3个月)的肿瘤样的细胞系只有少数报道。在这项研究中,我们从1例携带EML4-ALK的肺癌患者中建立了可以培养12个月的肿瘤样蛋白(PDT-LUAD#119).全外显子组测序和RNA测序分析显示TP53突变和EML4-ALKv3突变。PDT-LUAD#119肺类肿瘤对ALK酪氨酸激酶抑制剂（ALKTKIs）克唑替尼敏感，阿列替尼,恩替尼,和lorlatinib,类似于携带EML4-ALK变体1（v1）的NCI-H3122细胞。出乎意料的是,在PDT-LUAD#119肺肿瘤的异种移植物中观察到透明鳞状细胞癌和实体腺癌，提示腺鳞癌.免疫染色显示鳞状细胞癌为ALK阳性，提示腺癌的鳞状转化。除了提供一种新的癌症模型来支持ALK阳性肺癌的基础研究外，PDT-LUAD#119肺类肿瘤将有助于阐明腺鳞癌的发病机制。
