Identification of Copy Number Alterations From Shallow Whole-Genome Sequencing in Multiple Myeloma

Multiple myeloma (MM) is a malignant neoplasm of plasma cells leading to bone destruction and marrow failure. Prognosis and management of MM rely on cytogenetic determination of copy number alterations (CNAs). Nevertheless, karyotype analysis difficult due to the presence of few plasma cells and their low proliferative activity. A shallow whole-genome sequencing (sWGS) technology named LeukoPrint was used to detect genome-wide CNAs in MM patients (n = 128), which can cover the entire genome without involving cell culture. Compared with karyotyping and fluorescent in situ hybridization (FISH), LeukoPrint demonstrated a significantly higher detection rate of copy number alterations (CNAs), increasing from 8.0% (karyotyping) and 44.2% (FISH) to 75.0% (n = 96), provided new CNA information and redefined the prognostic stratification in 20.3% of patients according to mSMART guidelines. Hyperdiploidy was the most common CNA feature (39.6%) in this cohort. A high concordance of 90.7% was observed in CNA between matched bone marrow and peripheral blood samples. LeukoPrint 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, LeukoPrint can add value to conventional karyotyping with improved prognostic stratification.