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  • Korean Cancer Association  (4)
  • Kim, Ju Won  (4)
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  • Korean Cancer Association  (4)
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  • 1
    Online Resource
    Online Resource
    Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with That of Orthogonal Methods for Detecting Targetable Genetic Alterations
    Korean Cancer Association ; 2022
    In:  Cancer Research and Treatment Vol. 54, No. 1 ( 2022-01-15), p. 30-39
    Details
    In: Cancer Research and Treatment, Korean Cancer Association, Vol. 54, No. 1 ( 2022-01-15), p. 30-39
    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.
    Type of Medium: Online Resource
    ISSN: 1598-2998 , 2005-9256
    URL: Article
    DOI: 10.4143/crt.2021.218
    Language: English
    Publisher: Korean Cancer Association
    Publication Date: 2022
    detail.hit.zdb_id: 2514151-X
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  • 2
    Online Resource
    Online Resource
    Clinical Implication of Concordant or Discordant Genomic Profiling between Primary and Matched Metastatic Tissues in Patients with Colorectal Cancer
    Korean Cancer Association ; 2020
    In:  Cancer Research and Treatment Vol. 52, No. 3 ( 2020-07-15), p. 764-778
    Details
    In: Cancer Research and Treatment, Korean Cancer Association, Vol. 52, No. 3 ( 2020-07-15), p. 764-778
    Abstract: PurposeThe purpose of this study was to identify the concordant or discordant genomic profiling between primary and matched metastatic tumors in patients with colorectal cancer (CRC) and to explore the clinical implication.Materials and MethodsSurgical samples of primary and matched metastatic tissues from 158 patients (335 samples) with CRC at Korea University Anam Hospital were evaluated using the Ion AmpliSeq Cancer Hotspot Panel. We compared genetic variants and classified them as concordant, primary-specific, and metastasis-specific variants. We used a combination of principal components analysis and clustering to find genomic groups. Kaplan-Meier curves were used to appraise survival between genomic groups. We used machine learning to confirm the correlation between genetic variants and metastatic sites.ResultsA total of 282 types of deleterious non-synonymous variants were selected for analysis. Of a total of 897 variants, an average of 40% was discordant. Three genomic groups were yielded based on the genomic discrepancy patterns. Overall survival differed significantly between the genomic groups. The poorest group had the highest proportion of concordant 〈 i 〉 KRAS 〈 /i 〉 G12V and additional metastasis-specific 〈 i 〉 SMAD4 〈 /i 〉 . Correlation analysis between genetic variants and metastatic sites suggested that concordant 〈 i 〉 KRAS 〈 /i 〉 mutations would have more disseminated metastases.ConclusionDriver gene mutations were mostly concordant; however, discordant or metastasis-specific mutations were present. Clinically, the concordant driver genetic changes with additional metastasis-specific variants can predict poor prognosis for patients with CRC.
    Type of Medium: Online Resource
    ISSN: 1598-2998 , 2005-9256
    URL: Article
    DOI: 10.4143/crt.2020.044
    Language: English
    Publisher: Korean Cancer Association
    Publication Date: 2020
    detail.hit.zdb_id: 2514151-X
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  • 3
    Online Resource
    Online Resource
    Genomic Signatures from Clinical Tumor Sequencing in Patients with Breast Cancer Having Germline BRCA1/2 Mutation
    Korean Cancer Association ; 2023
    In:  Cancer Research and Treatment Vol. 55, No. 1 ( 2023-01-15), p. 155-166
    Details
    In: Cancer Research and Treatment, Korean Cancer Association, Vol. 55, No. 1 ( 2023-01-15), p. 155-166
    Abstract: Purpose 〈 i 〉 BRCA1 〈 /i 〉 and 〈 i 〉 BRCA2 〈 /i 〉 are among the most important genes involved in DNA repair via homologous recombination (HR). Germline 〈 i 〉 BRCA1/2 〈 /i 〉 ( 〈 i 〉 gBRCA1/2 〈 /i 〉 )-related cancers have specific characteristics and treatment options but conducting 〈 i 〉 gBRCA1/2 〈 /i 〉 testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of 〈 i 〉 gBRCA1/2 〈 /i 〉 derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring 〈 i 〉 gBRCA1/2 〈 /i 〉 pathogenic variants.Materials and MethodsTargeted sequencing was performed using available tumor tissue from patients who underwent 〈 i 〉 gBRCA1/2 〈 /i 〉 testing. Comparative genomic analysis was performed according to 〈 i 〉 gBRCA1/2 〈 /i 〉 pathogenicity.ResultsA total of 321 patients who underwent 〈 i 〉 gBRCA1/2 〈 /i 〉 testing were screened, and 26 patients with 〈 i 〉 gBRCA1/2 〈 /i 〉 pathogenic ( 〈 i 〉 gBRCA1/2p 〈 /i 〉 ) variants, eight patients with 〈 i 〉 gBRCA1/2 〈 /i 〉 variants of uncertain significance (VUS; 〈 i 〉 gBRCA1/2v 〈 /i 〉 ), and 43 patients with 〈 i 〉 gBRCA1/2 〈 /i 〉 wild-type ( 〈 i 〉 gBRCA1/2w 〈 /i 〉 ) were included in analysis. Mutations in 〈 i 〉 TP53 〈 /i 〉 (49.4%) and 〈 i 〉 PIK3CA 〈 /i 〉 (23.4%) were frequently detected in all samples. The number of single-nucleotide variants (SNVs) per tumor tissue was higher in the 〈 i 〉 gBRCA1/2w 〈 /i 〉 group than that in the 〈 i 〉 gBRCA1/2p 〈 /i 〉 group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the 〈 i 〉 gBRCA1/2w 〈 /i 〉 group than in the 〈 i 〉 gBRCA1/2p 〈 /i 〉 group (10.21 vs. 13.47, p=0.017). Except for 〈 i 〉 BRCA1/2 〈 /i 〉 , other HR-related genes were frequently mutated in patients with 〈 i 〉 gBRCA1/2w 〈 /i 〉 .ConclusionWe demonstrated high sensitivity of 〈 i 〉 gBRCA1/2 〈 /i 〉 in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non- 〈 i 〉 BRCA1/2 〈 /i 〉 HR-related genes differed significantly according to 〈 i 〉 gBRCA1/2 〈 /i 〉 pathogenicity in patients with breast cancer.
    Type of Medium: Online Resource
    ISSN: 1598-2998 , 2005-9256
    URL: Article
    DOI: 10.4143/crt.2021.1567
    Language: English
    Publisher: Korean Cancer Association
    Publication Date: 2023
    detail.hit.zdb_id: 2514151-X
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  • 4
    Online Resource
    Online Resource
    Clinical Application of Targeted Deep Sequencing in Metastatic Colorectal Cancer Patients: Actionable Genomic Alteration in K-MASTER Project
    Korean Cancer Association ; 2021
    In:  Cancer Research and Treatment Vol. 53, No. 1 ( 2021-01-15), p. 123-130
    Details
    In: Cancer Research and Treatment, Korean Cancer Association, Vol. 53, No. 1 ( 2021-01-15), p. 123-130
    Abstract: PurposeNext-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 MethodsAs 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.ResultsIn 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 〈 i 〉 BRAF 〈 /i 〉 V600E mutation (n=47, 4.7%), deficient mismatch repair/microsatellite instability–high (n=15, 1.5%), 〈 i 〉 HER2 〈 /i 〉 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 〈 i 〉 PIK3CA, KRAS 〈 /i 〉 G12C, atypical 〈 i 〉 BRAF 〈 /i 〉 , and 〈 i 〉 HER2 〈 /i 〉 mutations and even rarer but actionable genes that approved or ongoing clinical trials in other solid tumors.ConclusionK-MASTER project provides an intriguing background to investigate new clinical trials with biomarkers and give therapeutic opportunity for mCRC patients.
    Type of Medium: Online Resource
    ISSN: 1598-2998 , 2005-9256
    URL: Article
    DOI: 10.4143/crt.2020.559
    Language: English
    Publisher: Korean Cancer Association
    Publication Date: 2021
    detail.hit.zdb_id: 2514151-X
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