title: Genomic complexity of multiple myeloma and its clinical implications.
abstract: Multiple myeloma (MM) is a genetically complex disease that evolves from pre-malignant stages, such as monoclonal gammaopathy of undetermined significance and smouldering multiple myeloma, and progresses to symptomatic MM; this continuum provides a unique framework to study the sequential genomic evolution of MM. In the past 5 years, results from large-scale whole-exome sequencing studies have provided new insights into the clonal heterogeneity and evolution of the disease. Moreover, the recurrent co-occurrence of genomic events helps to dissect the genomic complexity underlying tumour progression. According to the primary genetic events involved in tumorigenesis, MM tumours are hierarchically subdivided into hyperdiploid and non-hyperdiploid subtypes; subsequently, secondary genetic events lead to tumour progression. In this Review, we describe the 'driver' gene alterations involved in the development and progression of MM, with a focus on the sequential acquisition of the main genomic aberrations. We also provide valuable insight into the clonal heterogeneity and clonal evolution of the disease, as well as into the therapeutic implications of a comprehensive understanding of the genomic complexity of MM.
authors.affiliation: Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, HIM 237, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.|Cancer Program, Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA.
authors.forename: Salomon
authors.initials: S
authors.lastname: Manier
authors.affiliation: Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, HIM 237, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.|Cancer Program, Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA.
authors.forename: Karma Z
authors.initials: KZ
authors.lastname: Salem
authors.affiliation: Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, HIM 237, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.|Cancer Program, Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA.
authors.forename: Jihye
authors.initials: J
authors.lastname: Park
authors.affiliation: New York Genome Center, 101 Avenue of the Americas, Room 621, New York, New York 10013, USA.|Weill Cornell Medicine, Belfer Research Building, Room 1428, New York, New York 10021, USA.
authors.forename: Dan A
authors.initials: DA
authors.lastname: Landau
authors.affiliation: Cancer Program, Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA.|Cancer Center and Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, USA.
authors.forename: Gad
authors.initials: G
authors.lastname: Getz
authors.affiliation: Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, HIM 237, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.|Cancer Program, Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
mesh_terms: D002872:Chromosome Deletion; D060965:Clonal Evolution / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D004171:Diploidy; D018740:Genetic Heterogeneity; D005819:Genetic Markers / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D005819:Genetic Markers