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Ultra‐low depth sequencing of plasma cell DNA for the detection of copy number aberrations in multiple myeloma
Author(s) -
Buedts Lieselot,
Smits Sanne,
Ameye Geneviève,
Lehnert Stefan,
Ding Jia,
Delforge Michel,
Vermeesch Joris,
Boeckx Nancy,
Tousseyn Thomas,
Michaux Lucienne,
Vandenberghe Peter,
Dewaele Barbara
Publication year - 2020
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22848
Subject(s) - copy number analysis , multiple myeloma , dna sequencing , fish <actinopterygii> , biology , comparative genomic hybridization , copy number variation , computational biology , genome , plasma cell myeloma , microbiology and biotechnology , genetics , dna , gene , immunology , fishery
Cytogenetic abnormalities are powerful prognostic factors in multiple myeloma (MM) and are routinely analyzed by FISH on bone marrow (BM) plasma cells (PC). Although considered the gold standard, FISH experiments can be laborious and expensive. Therefore, array‐CGH (aCGH) has been introduced as an alternative approach for detecting copy number aberrations (CNA), reducing the number of FISH experiments per case and yielding genome‐wide information. Currently, next generation sequencing (NGS) technologies offer new perspectives for the diagnostic workup of malignant disorders. In this study, we examined ultra‐low depth whole genome sequencing (LDS) as a valid alternative for aCGH for the detection of CNA in BM PC in MM. To this end, BM aspirates obtained in a diagnostic setting from 20 MM cases were analyzed. CD138+ cell‐sorted samples were subjected to FISH analysis. DNA was extracted for subsequent aCGH and LDS analysis. CNA were detected by aCGH and LDS in all but one case. Importantly, all CNA identified by parallel first generation aCGH analysis were also detected by LDS, along with six additional CNA in five cases. One of these additional aberrations was in a region of prognostic importance in MM and was confirmed using FISH. However, risk stratification in these particular cases was unaffected. Thus, a perfectly concordant prognostication between array‐CGH and LDS was observed. This validates LDS as a novel and cost‐efficient tool for the detection of CNA in MM.