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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.
ABSTRACT
Purpose@#Next-generation sequencing (NGS) can facilitate precision medicine approaches in metastatic colorectal cancer (mCRC) patients. We investigated the molecular profiling of Korean mCRC patients under the K-MASTER project which was initiated in June 2017 as a nationwide precision medicine oncology clinical trial platform which used NGS assay to screen actionable mutations. @*Materials and Methods@#As of 22 January 2020, total of 994 mCRC patients were registered in K-MASTER project. Targeted sequencing was performed using three platforms which were composed of the K-MASTER cancer panel v1.1 and the SNUH FIRST Cancer Panel v3.01. If tumor tissue was not available, cell-free DNA was extracted and the targeted sequencing was performed by Axen Cancer Panel as a liquid biopsy. @*Results@#In 994 mCRC patients, we found 1,564 clinically meaningful pathogenic variants which mutated in 71 genes. Anti-EGFR therapy candidates were 467 patients (47.0%) and BRAF V600E mutation (n=47, 4.7%), deficient mismatch repair/microsatellite instability–high (n=15, 1.5%), HER2 amplifications (n=10, 1.0%) could be incorporated with recently approved drugs. The patients with high tumor mutation burden (n=101, 12.7%) and DNA damaging response and repair defect pathway alteration (n=42, 4.2%) could be enrolled clinical trials with immune checkpoint inhibitors. There were more colorectal cancer molecular alterations such as PIK3CA, KRAS G12C, atypical BRAF, and HER2 mutations and even rarer but actionable genes that approved or ongoing clinical trials in other solid tumors. @*Conclusion@#K-MASTER project provides an intriguing background to investigate new clinical trials with biomarkers and give therapeutic opportunity for mCRC patients.
ABSTRACT
BACKGROUND: The accumulation of lipoprotein and monocyte in the intima of the arterial wall is the most important step of the development of coronary artery disease (CAD). Lipoprotein lipase (LPL) plays an anti-atherogenic role by lipolysis of triglyceride-rich lipoproteins, but, it may also act as a receptor of some lipoproteins and monocyte at the arterial wall and act as a atherogenic molecule. Previous studies showed somewhat contradictory results about the association of CAD and LPL polymorphisms and mutations. Racial and dietary difference may contribute to these contradictory results. In this study, we tried to find out the association of CAD and the genetic variation of the LPL (PvuII RFLP in intron 6, HindIII RFLP in intron 8 and Ser 447 Ter mutation in exon 9) in Korean population. METHOD AND RESULT: CAD patients (n=146), confirmed by coronary angiography and healthy Korean adult volunteers (n=110) were genotyped for PvuII/HindIII RFLP and Ser447Ter mutation of the LPL gene by PCR-digestion method. Between two groups, the genotype frequency of these genetic variations was not different. But, the genetic variations showed different effect on lipid profile and body mass index (BMI) in the CAD group and in the control group. In the CAD group, P1 allele carriers showed higher total cholesterol (P1P1+P1P2:P2P2=216+-51 mg/dl:198+/-38 mg/dl, p=0.039) and higher LDL cholesterol level (P1P1+P1P2:P2P2=143+/-46 mg/dl:126+/-36 mg/dl, p=0.047), and H1 allele carriers had lower Body mass index than non-carriers (23.8+/-2.3 kg/m2 :24.8+/-2.9 kg/m2 , p=0.047). In the control group, the Ser447Ter mutation carriers had higher HDL cholesterol level than non-carriers (59+/-10mg/dl versus 53+/-11mg/dl, p=0.049) and patients with P1 allele showed lower body mass index (P1P1+P1P2: P2P2=23.1+/-2.6 kg/m 2 :24.5+/-2.6 kg/m2 , p=0.006). CONCLUSION: In Korean, PvuII/HindIII RFLP and Ser447Ter mutation was not associated with CAD, and they showed different effect on the lipid profile and on the body mass index according to the study group. These results suggests that the phenotypic characteristics of the LPL gene of the Korean people are different from those of occidental people.