期刊
CANCER RESEARCH AND TREATMENT
卷 55, 期 2, 页码 429-441出版社
KOREAN CANCER ASSOCIATION
DOI: 10.4143/crt.2022.891
关键词
High-throughput nucleotide sequencing; DNA mutational analysis; Genetic testing; Validation; Neoplasms
类别
The purpose of this study was to validate a targeted hybridization capture-based DNA panel (ONCOaccuPanel) for the simultaneous detection of genetic alterations in solid tumors using the Illumina MiSeq sequencing platform. The panel showed high sensitivity, reproducibility, and repeatability in detecting clinically relevant mutations, as demonstrated through validation using known genetic mutations and additional sequencing of tumor samples. The clinical application of ONCOaccuPanel also showed robust detection of oncogenic alterations and targetable genetic alterations in a significant percentage of cases.
Purpose Targeted next-generation sequencing (NGS) is widely used for simultaneously detecting clinically informative genetic alterations in a single assay. Its application in clinical settings requires the validation of NGS gene panels. In this study, we aimed to validate a targeted hybridization capture-based DNA panel (ONCOaccuPanel) using the Illumina MiSeq sequencing platform. The panel allows the simultaneous detection of single-nucleotide variants (SNVs), insertions, deletions, and copy number changes of 323 genes and fusions of 17 genes in solid tumors. Materials and Methods We used 16 formalin-fixed paraffin-embedded (FFPE) tumor samples with previously known genetic mutations and one reference material (HD827) for validation. Moreover, we sequenced an additional 117 FFPE tumor samples to demonstrate the clinical utility of this panel. Results Validation revealed a 100% positive percentage agreement and positive predictive value for the detection of SNVs, insertions, deletions, copy number changes, fusion genes, and microsatellite instability-high types. We observed high levels of reproducibility and repeatability (R2 correlation coefficients=0.96-0.98). In the limit of detection assessment, we identified all clinically relevant genes with allele frequencies > 3%. Furthermore, the clinical application of ONCOaccuPanel using 117 FFPE samples demonstrated robust detection of oncogenic alterations. Oncogenic alterations and targetable genetic alterations were detected in 98.2% and 27.4% cases, respectively. Conclusion ONCOaccuPanel demonstrated high analytical sensitivity, reproducibility, and repeatability and is feasible for the detection of clinically relevant mutations in clinical settings.
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