Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan.
Department of Surgery, Tokyo Medical University, Tokyo, Japan.
Cancer Sci. 2019 Jun;110(6):2044-2049. doi: 10.1111/cas.14016. Epub 2019 May 3.
Gene fusions play an important role in the carcinogenesis of lung adenocarcinoma. The recent association of four oncogenic driver genes, ALK, ROS1, RET, and NTRK1, as lung tumor predictive biomarkers has increased the need for precision medicine. We used formalin-fixed, paraffin-embedded tissue samples of non-small cell lung cancer from 150 EGFR mutation-negative cases and 10 fusion status-known cases and compared the performance of the Oncomine Dx Fusion Transcript Test (ODxFT) with FISH break-apart for the detection of ALK, RET, and ROS1 fusion genes. RNA was extracted from the paraffin-embedded tissue samples with or without macrodissection under hematoxylin and eosin staining, and the ALK fusion gene was independently determined using these assays. Fusion detection analyses were successfully carried out using ODxFT in 150 cases, with only one invalid case. ALK fusion genes were detected at a frequency of 7.3% (11/150) in the lung cancer specimens. Concordance rate between the ODxFT and ALK-FISH analyses was 99.3% (148/149). Sensitivity and specificity were 91.7% and 99.3%, respectively. All the samples with a known fusion status were accurately matched between the two assays. Our results show a high concordance rate between the ODxFT and ALK-FISH analyses. ODxFT was thus validated as an effective method for detecting clinically significant ALK fusion genes in paraffin-embedded tissue samples.
基因融合在肺腺癌的致癌作用中发挥着重要作用。最近，ALK、ROS1、RET 和 NTRK1 这四个致癌驱动基因作为肺肿瘤预测生物标志物的关联，增加了对精准医疗的需求。我们使用了 150 例 EGFR 突变阴性病例和 10 例融合状态已知病例的福尔马林固定、石蜡包埋的非小细胞肺癌组织样本，并比较了 Oncomine Dx Fusion Transcript Test (ODxFT) 与 FISH 分离法检测 ALK、RET 和 ROS1 融合基因的性能。从有或无苏木精和伊红染色的大体解剖的石蜡包埋组织样本中提取 RNA，并使用这些检测方法独立确定 ALK 融合基因。ODxFT 成功地对 150 例病例进行了融合检测分析，仅有 1 例无效。在肺癌标本中，ALK 融合基因的检出率为 7.3%（11/150）。ODxFT 与 ALK-FISH 分析的一致性率为 99.3%（148/149）。灵敏度和特异性分别为 91.7%和 99.3%。两种检测方法在所有已知融合状态的样本中均能准确匹配。我们的结果表明，ODxFT 与 ALK-FISH 分析之间具有很高的一致性。因此，ODxFT 被验证为一种在石蜡包埋组织样本中检测临床显著的 ALK 融合基因的有效方法。
