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Clinical Utility of Targeted Next-Generation Sequencing Assay to Detect Copy Number Variants in Myeloid Malignancies: Is It Ready for Prime Time?

ABSTRACT: Genetic abnormalities including copy number variants (CNVs, such as gains and losses), and gene mutations are important for diagnosis and treatment of myeloid malignances. In a routine clinical setting, somatic gene mutations are detected by targeted next generation sequencing (NGS), but CNVs are commonly detected by conventional chromosome analysis and fluorescence in situ hybridization (FISH). The aim of this proof-of-principle study was to investigate the feasibility of using a targeted NGS assay to simultaneously detect not only somatic mutations, but also CNVs. Here, we sequenced 406 consecutive patients with myeloid malignancies and performed a head-to-head comparison with the results from conventional clinical assays including conventional chromosome analysis and myeloid FISH to detect CNVs. The targeted NGS assay revealed all 120 CNVs detected by myeloid FISH panel including monosomy 5/5q deletions, monosomy 7/7q deletions, trisomy 8, and 20q deletions. Furthermore, the targeted NGS assay also detected 605 CNVs outsides targeted regions of the myeloid FISH panel, which were revealed by conventional cytogenetic testing. The targeted NGS assay achieved 100% concordance with the myeloid FISH for detection of these common myeloid CNVs, with a high clinical sensitivity (> 99%) and specificity (>99%). The lower limit of detection by the myeloid FISH and the targeted NGS assay was similar and was generally 5% variant allele fraction for DNA. This proof-of-principle study demonstrated that the targeted NGS assay can simultaneously detect both common myeloid CNVs and somatic mutations, which can provide more comprehensive genetic profiling for patients with myeloid malignancies using a single assay.

ORGANISM(S): Homo sapiens

PROVIDER: GSE165733 | GEO | 2021/01/29

REPOSITORIES: GEO

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Clinical Utility of Targeted Next-Generation Sequencing Assay to Detect Copy Number Variants in Myeloid Malignancies: Is It Ready for Prime Time?

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