Immunomagnetic bead selection

Patient samples were collected after informed consent and using protocols approved by an ethical committee of the Helsinki University Hospital (permit numbers 239/13/03/00/2010, 303/13/03/01/2011) in accordance with the Declaration of Helsinki. In total, 178 (NDMM, n = 57; RRMM, n = 121) different patient samples were collected from 140 different MM patients (Table 1, Online Supplementary Table S1). Bone marrow mononuclear cells (BM-MNCs) were isolated from BM aspirates by Ficoll-Paque gradient centrifugation (GE Healthcare, Little Chalfont, Buckinghamshire, UK). For RNA and exome sequencing, BM CD138+ plasma cells were enriched by immunomagnetic bead selection (StemCell Technologies, Vancouver, BC, Canada).

For gene expression profiling and evaluation of genomic variants in the Institute for Molecular Medicine Finland (FIMM) cohort, bone marrow aspirates were obtained from multiple myeloma patients after obtaining written informed consent and following protocols approved by an ethical committee of the Helsinki University Hospital Comprehensive Cancer Center, and in compliance with the Declaration of Helsinki. Matched patient skin biopsies were collected (also with informed consent) at the same time and from the same site as bone marrow aspirates, and in accordance with approved protocols, for constitutional DNA analysis. Bone marrow mononuclear cells were isolated by Ficoll-Paque gradient centrifugation (GE Healthcare), and CD138+ plasma cells enriched by immuno-magnetic bead selection (StemCell Technologies).