RT Journal Article
SR Electronic
T1 Detection of genome-wide copy number variants in myeloid malignancies using next-generation sequencing
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP jclinpath-2017-204823
DO 10.1136/jclinpath-2017-204823
A1 Wei Shen
A1 Christian N Paxton
A1 Philippe Szankasi
A1 Maria Longhurst
A1 Jonathan A Schumacher
A1 Kimberly A Frizzell
A1 Shelly M Sorrells
A1 Adam L Clayton
A1 Rakhi P Jattani
A1 Jay L Patel
A1 Reha Toydemir
A1 Todd W Kelley
A1 Xinjie Xu
YR 2017
UL http://jcp.bmj.com/content/early/2017/12/02/jclinpath-2017-204823.abstract
AB Aims Genetic abnormalities, including copy number variants (CNV), copy number neutral loss of heterozygosity (CN-LOH) and gene mutations, underlie the pathogenesis of myeloid malignancies and serve as important diagnostic, prognostic and/or therapeutic markers. Currently, multiple testing strategies are required for comprehensive genetic testing in myeloid malignancies. The aim of this proof-of-principle study was to investigate the feasibility of combining detection of genome-wide large CNVs, CN-LOH and targeted gene mutations into a single assay using next-generation sequencing (NGS).Methods For genome-wide CNV detection, we designed a single nucleotide polymorphism (SNP) sequencing backbone with 22 762 SNP regions evenly distributed across the entire genome. For targeted mutation detection, 62 frequently mutated genes in myeloid malignancies were targeted. We combined this SNP sequencing backbone with a targeted mutation panel, and sequenced 9 healthy individuals and 16 patients with myeloid malignancies using NGS.Results We detected 52 somatic CNVs, 11 instances of CN-LOH and 39 oncogenic mutations in the 16 patients with myeloid malignancies, and none in the 9 healthy individuals. All CNVs and CN-LOH were confirmed by SNP microarray analysis.Conclusions We describe a genome-wide SNP sequencing backbone which allows for sensitive detection of genome-wide CNVs and CN-LOH using NGS. This proof-of-principle study has demonstrated that this strategy can provide more comprehensive genetic profiling for patients with myeloid malignancies using a single assay.