为了分析ALK融合基因伴侣、基因亚型和在ALK融合阳性晚期非小细胞肺癌（NSCLC）患者肿瘤组织中的丰度特征和预后价值，并探索最佳的ALK酪氨酸激酶抑制剂（TKIs）治疗模式。回顾性收集ALK阳性经Next Generation Sequencing（NGS）和免疫组化确诊的晚期NSCLC患者病例。分析不同突变亚型、突变丰度、临床病理特征与总生存期（OS）/无进展生存期（PFS）之间的关系。比较不同ALK抑制剂治疗模式之间的OS/PFS。共纳入58例患者，融合伴侣多样化。检测到Echinoderm Microtubule-associated protein-Like 4基因（EML4）-ALK融合突变的五个亚型：V1，V2，V3，V5和V7。突变丰度范围从0.13%到27.77%，中位数为5.34%。V2和V5的丰度高于V1和V3。低丰度组（≤5.34%）和高丰度组（>5.34%）之间的OS无差异（P=0.434）。二代ALK抑制剂作为一线治疗的PFS比克黄咽苏片（Crizotinib）作为一线治疗更长（P<0.001）。非吸烟者的OS比吸烟者长（P=0.001）。ALK阳性晚期NSCLC中不同融合伴侣和亚型的丰度存在差异。OS与亚型、突变丰度以及ALK抑制剂的一线治疗选项无关。吸烟是不良预后因素。© 2023 BioMed Central Ltd., part of Springer Nature.

To analyze the characteristics and prognostic values of Anaplastic Lymphoma Kinase (ALK) fusion gene partner, gene subtype and abundance in tumor tissues of advanced Non Small Cell Lung Cancer (NSCLC) patients with positive ALK fusion gene and to explore the best treatment mode of ALK-Tyrosine Kinase Inhibitors(TKIs).Cases of advanced NSCLC patients with ALK positive confirmed by both Next Generation Sequencing (NGS) and immunohistochemistry were retrospectively collected. The relationships of Overall Survival (OS)/Progression Free Survival (PFS) between different mutation subtypes, mutation abundance, clinicopathological features were analyzed. OS/PFS between different treatment mode of ALK inhibitors were compared.Fifty-eight patients were enrolled. There were diverse fusion partners. Five subtypes of Echinoderm Microtubule-associated protein-Like 4 gene (EML4)-ALK fusion mutation were detected: V1,V2,V3,V5 and V7. The mutation abundance ranged from 0.13 to 27.77%, with a median of 5.34%. The abundance of V2 and V5 was higher than V1 and V3 respectively. There was no difference in OS between the low abundance group(≤ 5.34%) and the high abundance group(>5.34%) (P = 0.434). PFS of second-generation ALK inhibitors as first-line treatment was longer than that of Crizotinib as first-line (P<0.001). Never smokers had longer OS than current smokers(P = 0.001).There are differences in abundance between different fusion partners and subtypes in advanced NSCLC with positive ALK. OS is not associated with subtypes, mutation abundance and first line treatment option of either generation of ALK inhibitors. Smoking is a poor prognostic factor.© 2023. BioMed Central Ltd., part of Springer Nature.