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

Abstract

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 MethodsColorectal, 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); EGFR, ALK fusion, and ROS1 fusion in non-small-cell lung cancer (NSCLC), and ERBB2 positivity in breast and gastric cancers). ResultsIn 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. ConclusionThe 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.

Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group

“…To further improve molecular profiling guided therapy, development of better decision-making aids based on the Korean health care situation is needed, as well as a platform for shared decision-making with patients and families [ 34 – 36 ]. Furthermore, it will be essential to build a nationwide clinico-genomic database, integrating genomic data and clinical data including tumor and patient characteristics, prescription data with corresponding treatment outcomes including survival [ 37 – 39 ]. Data privacy protection and appropriate data-sharing strategies should be accompanied to make clinico-genomic database usable to all stakeholders for future research, drug development, practice, drug approval, and reimbursement.…”

Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer

“…Targeted sequencing using tumor tissues were performed using CancerSCAN™ (Samsung Genome Institute, Seoul, Korea) which encompasses the exons of 396 human cancer related genes (Supplementary Table S12 ). In the case of ctDNA analysis, we utilized the K-Master Axen™ Cancer Panel (Macrogen, Seoul, Korea) targeting the exons of 89 human cancer related genes (Supplementary Table S13 ) 41 . DNA input for generate sequencing library was 200 ng for FFPE and 10 ng for ctDNA samples.…”