Genomic characterization of patient derived xenograft models of multiple myeloma reveals selection of multiple pre-existing high risk clones

SCID-rab patient-derived xenografts expanded scarce primary multiple myeloma samples across disease stages and cytogenetic subgroups while retaining genomic, transcriptomic and proteomic features of the patient tumors, including abundant CD138+ cells. WGS and single-cell WGS showed the xenografts arose by selection of pre-existing subclones, some harboring high-risk alterations and convergent tumor suppressor inactivation. The models also matched primary MM more closely than myeloma cell lines in proliferative state and therapeutic target expression.