Ultradeep, targeted sequencing reveals distinct mutations in blood compared to matched bone marrow among patients with multiple myeloma

Multiple myeloma (MM) is an incurable plasma cell neoplasm that evolves from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Primary genomic events responsible for the development of MGUS and SMM include hyperdiploidy, translocations, and copy number alterations 1 . Secondary events causing the transformation to active MM are driven by the acquisition of somatic mutations, including single-nucleotide variants (SNVs) and insertions and deletions (indels) 1 . Large-scale genomic studies, primarily of newly diagnosed MM, have identified at least 65 significant, recurrently mutated genes affecting 5 distinct cellular pathways 1 , 2 .