Abstract
Multiple myeloma (MM) is an incurable hematological malignancy that relies on cytogenetic determination of copy number abnormalities (CNAs) for prognosis and management. Low-depth whole genome sequencing (LD-WGS) is a cost-effective alternative to targeted genomics for CNA detection, but its value has yet to be explored in MM. DNA from CD138+ cells from MM patients were sequenced using an Illumina NextSeq at <1x depth (ultralow-depth). Subsampling analysis and window size adjustment were performed for determining sensitivity limits and results compared to fluorescent in-Situ hybridization (FISH). CNA calls made down to 5 million (M) reads were comparable to those at 20 M reads at a window size of 100 kb had a sensitivity and specificity of 93%, 92% and an area under the curve of 0.94. All CNAs detected by FISH on the MM samples were also detected by LD-WGS; the latter detected a further 36 focal CNAs not detected by FISH. Cost per sample of LD-WGS was significantly lower for our organization than FISH testing. LD-WGS for MM is significantly more sensitive than targeted technologies such as FISH in CNA detection and resolution, provides a more cost-effective option for clinical purposes and potential for exploring prognostically relevant and drug discovery targets.
Original language | English |
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Pages (from-to) | 163-168 |
Number of pages | 6 |
Journal | Clinical Genetics |
Volume | 96 |
Issue number | 2 |
DOIs | |
Publication status | Published - Aug 2019 |
Bibliographical note
Funding Information:We thank Makoto Matsuoka, Judy Park and Kendra MacDonald for excellent technical assistance and the Molecular Diagnostics Laboratory at the IWK Hospital for their valuable assistance. This study was supported by a Nova Scotia Health Authority Research grant (#1021270). Illumina provided the reagents for library preparation and flow cell for sequencing.
Publisher Copyright:
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
ASJC Scopus Subject Areas
- Genetics
- Genetics(clinical)