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Low‐depth sequencing for copy number abnormalities in multiple myeloma supersedes fluorescent in situ hybridization in scope and resolution
Author(s) -
Elnenaei Manal O.,
Knopf Philipp,
Cutler Samuel D.,
Sinclair Keaton,
Abou El Hassan Mohamed,
Greer Wenda,
Goudie Marissa,
Wagner Julie,
White Darrell,
Couban Stephen,
Forward Nicholas,
Gaston Daniel,
Campbell Clinton J.V.
Publication year - 2019
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13561
Subject(s) - fluorescence in situ hybridization , fish <actinopterygii> , biology , multiple myeloma , genome , malignancy , dna sequencing , whole genome sequencing , computational biology , genetics , microbiology and biotechnology , dna , gene , immunology , fishery , chromosome
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.