目的:K-MASTER项目是韩国国家精准医学平台,通过分析实体瘤患者的下一代测序(NGS)来筛选可操作的突变。我们比较了来自K-MASTER项目的NGS面板和正交方法之间的基因分析。
方法:结直肠,乳房,非小细胞肺,包括胃癌患者。我们比较了K-MASTER项目的NGS结果与非NGS正交方法的结果(KRAS,NRAS,和BRAF突变在结直肠癌[CRC];表皮生长因子受体[EGFR],间变性淋巴瘤激酶[ALK]融合,和活性氧1[ROS1]融合在非小细胞肺癌[NSCLC]中,和Erb-B2受体酪氨酸激酶2(ERBB2)在乳腺癌和胃癌中的阳性)。
结果:在CRC队列中(n=225),NGS的敏感性和特异性分别为87.4%和79.3%(KRAS);88.9%和98.9%(NRAS);77.8%和100.0%(BRAF),分别。在NSCLC队列中(n=109),NGS对EGFR的敏感性和特异性分别为86.2%和97.5%,分别。ALK融合的一致率为100%,但在正交试验中3例阳性的病例中只有1例ROS1融合阳性。在乳腺癌队列中(n=260),ERBB2扩增在NGS检测到45。与结合免疫组织化学和原位杂交的正交方法相比,敏感性和特异性分别为53.7%和99.4%,分别。在胃癌队列中(n=64),ERBB2扩增检测到6个NGS。与正交方法相比,敏感性和特异性分别为62.5%和98.2%,分别。
结论:K-MASTERNGS小组和正交方法的结果表明,每种遗传改变的一致性程度不同,但总体上表现出很高的协议率。
OBJECTIVE: K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods.
METHODS: Colorectal, breast, non-small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non-small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers).
RESULTS: In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively.
CONCLUSIONS: The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.