比较 K-MASTER 项目下一代测序 panel 的数据与其他检测靶向遗传改变的正交方法的数据。

Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with That of Orthogonal Methods for Detecting Targetable Genetic Alterations.

机构信息

Division of Oncology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.

Cancer Precision Medicine Diagnosis and Treatment Enterprise, Korea University Anam Hospital, Seoul, Korea.

出版信息

Cancer Res Treat. 2022 Jan;54(1):30-39. doi: 10.4143/crt.2021.218. Epub 2021 May 20.

DOI:10.4143/crt.2021.218

PMID:34015890

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8756135/

Abstract

PURPOSE

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.

MATERIALS AND 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.

CONCLUSION

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.

摘要

目的

K-MASTER 项目是一个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）筛选可操作的突变。我们比较了 K-MASTER 项目的 NGS 面板与正交方法之间的基因分析。

材料和方法

纳入结直肠癌、乳腺癌、非小细胞肺癌和胃癌患者。我们比较了 K-MASTER 项目的 NGS 结果与非 NGS 正交方法（结直肠癌中的 KRAS、NRAS 和 BRAF 突变；非小细胞肺癌中的表皮生长因子受体 [EGFR]、间变性淋巴瘤激酶 [ALK] 融合和活性氧 1 [ROS1] 融合，以及乳腺癌和胃癌中的 Erb-B2 受体酪氨酸激酶 2 [ERBB2] 阳性）的结果。

结果

在结直肠癌队列（n=225）中，NGS 的敏感性和特异性分别为 87.4%和 79.3%（KRAS）；88.9%和 98.9%（NRAS）；和 77.8%和 100.0%（BRAF）。在非小细胞肺癌队列（n=109）中，NGS 检测 EGFR 的敏感性和特异性分别为 86.2%和 97.5%。ALK 融合的一致性率为 100%，但 ROS1 融合仅在正交检测阳性的三个病例中的一个中呈阳性。在乳腺癌队列（n=260）中，NGS 检测到 45 例 ERBB2 扩增。与整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%。在胃癌队列（n=64）中，NGS 检测到 6 例 ERBB2 扩增。与正交方法相比，敏感性和特异性分别为 62.5%和 98.2%。