Copy Number Variants Identified By Shallow Whole-Genome Sequencing in Multiple Myeloma

Background:

Multiple myeloma is a plasma cell neoplasm driven by primary and secondary chromosomal events. The detection of these copy number abnormalities (CNAs) are important, because they affect the prognosis, therapeutic response and disease survival.

Methods:

A total of 131 patients with newly diagnosed multiple myeloma were enrolled in this study to detect genome-wide CNAs by shallow whole-genome sequencing(sWGS). Risk stratification was performed following the Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART) criteria.

Results:

Compared with karyotyping and Fluorescence in situ hybridization (FISH), sWGS

significantly improved the detection rate of CNAs from 7.8% and 43.7%, respectively, to 75.6%. sWGS provided new CNA information for 75.6% of the patients, and changed the risk stratification for 19.1% of patients according to mSMART criteria. The concordance rate between sWGS and FISH in detecting the four conventional loci (1q21 gain, 13q14 del, 13q14.3 del, and 17p13 del) was 80.2%. A high concordance was observed in CNA between matched bone marrow and peripheral blood samples.

Conclusion:

sWGS can be regarded as an automated, convenient and cost-effective approach to describe genomic CNA profiles. With the advantage of detecting CNAs of short segments and incorporating routine diagnostic methods, sWGS can add value to conventional karyotyping with improved prognostic stratification.

No relevant conflicts of interest to declare.