A Novel Integrated Approach for Cytogenomic Evaluation of Plasma Cell Neoplasms

Plasma cell neoplasm (PCN) is associated with characteristic chromosomal aberrations of diagnostic and prognostic significance. The presence of a small percentage of neoplastic cells is a drawback in the application of karyotyping and fluorescence in situ hybridization for the evaluation of bone marrow aspirate. The analysis of samples enriched for CD138⁺ cells has improved the detection rate. However, fluorescence in situ hybridization requires several probes and may not be completed due to a limited number of isolated cells. To address the issues experienced with the conventional approach, a novel integrated protocol that consists of whole-genome amplification of DNA isolated from CD138⁺ cells, followed by microarray as well as one fluorescence in situ hybridization assay for balanced IGH gene rearrangements, has been developed. In the present study in a cohort of 56 patients with clinical suspicion for PCN, compared to conventional cytogenetic analysis, this approach provided higher yield in the detection of PCN-related abnormalities, irrespective of the initial percentage of plasma cells. Whole-genome profiling uncovered recurrent chromosomal abnormalities of prognostic value, including unbalanced alterations within the MYC locus, 16q loss, and hypodiploidy, that were not otherwise detectable by conventional methods. The proposed approach is cost-efficient and provides a superior detection rate, required for proper risk stratification and differential diagnosis of PCN regardless of initial plasma cell percentage.