Clinical Utility of Targeted Next-Generation Sequencing Assay to Detect Copy Number Variants Associated with Myelodysplastic Syndrome in Myeloid Malignancies

Liqun Jiang, Aparna Pallavajjalla, Jialing Huang, Lisa Haley, Laura Morsberger, Victoria Stinnett, Melanie Hardy, Rebecca Park, Candice Ament, Alexandra Finch, Alison Shane, Rebecca Parish, Azin Nozari, Patty Long, Emily Adams, Kirstin Smith, Vamsi Parimi, Sam Dougaparsad, Lori Long, Christopher D. GockeYing S. Zou

Research output: Contribution to journalArticlepeer-review

Abstract

Copy number variants (CNVs) and gene mutations are important for diagnosis and treatment of myeloid malignancies. In a routine clinical setting, somatic gene mutations are detected by targeted next-generation sequencing (NGS) assay, 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 targeted NGS to simultaneously detect both somatic mutations and CNVs. Herein, we sequenced 406 consecutive patients with myeloid malignancies by targeted NGS and performed a head-to-head comparison with the results from a myelodysplastic syndrome (MDS) FISH and conventional chromosome analysis to detect CNVs. Among 91 patients with abnormal MDS FISH results, the targeted NGS revealed all 120 CNVs detected by MDS FISH (including −5/5q−, −7/7q−, +8, and 20q−) and 193 extra CNVs detected by conventional chromosome analysis. The targeted NGS achieved 100% concordance with the MDS FISH. The lower limit of detection of MDS CNVs by the targeted NGS was generally 5% variant allele fraction for DNA, based on the lowest percentages of abnormal cells detected by MDS FISH in this study. This proof-of-principle study demonstrated that the targeted NGS assay can simultaneously detect both MDS CNVs and somatic mutations, which can provide a more comprehensive genetic profiling for patients with myeloid malignancies using a single assay in a clinical setting.

Original languageEnglish (US)
Pages (from-to)467-483
Number of pages17
JournalJournal of Molecular Diagnostics
Volume23
Issue number4
DOIs
StatePublished - Apr 2021

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine

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