title: Mechanisms and Clinical Applications of Genome Instability in Multiple Myeloma.
abstract: Ongoing genomic instability represents a hallmark of multiple myeloma (MM) cells, which manifests largely as whole chromosome- or translocation-based aneuploidy. Importantly, although it supports tumorigenesis, progression and, response to treatment in MM patients, it remains one of the least understood components of malignant transformation in terms of molecular basis. Therefore these aspects make the comprehension of genomic instability a pioneering strategy for novel therapeutic and clinical speculations to use in the management of MM patients. Here we will review mechanisms mediating genomic instability in MM cells with an emphasis placed on pathogenic mutations affecting DNA recombination, replication and repair, telomere function and mitotic regulation of spindle attachment, centrosome function, and chromosomal segregation. We will discuss the mechanisms by which genetic aberrations give rise to multiple pathogenic events required for myelomagenesis and conclude with a discussion of the clinical applications of these findings in MM patients.
authors.affiliation: Hematology Unit, Department of Internal Medicine (DiMI), University of Genoa, IRCCS AOU San Martino-IST, 1600 Genoa, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Cagnetta
authors.affiliation: Hematology Unit, Department of Internal Medicine (DiMI), University of Genoa, IRCCS AOU San Martino-IST, 1600 Genoa, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Lovera
authors.affiliation: Hematology Unit, Department of Internal Medicine (DiMI), University of Genoa, IRCCS AOU San Martino-IST, 1600 Genoa, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Grasso
authors.affiliation: Hematology Unit, Department of Internal Medicine (DiMI), University of Genoa, IRCCS AOU San Martino-IST, 1600 Genoa, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Colombo
authors.affiliation: Hematology Unit, Department of Internal Medicine (DiMI), University of Genoa, IRCCS AOU San Martino-IST, 1600 Genoa, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Canepa
authors.affiliation: Hematology Unit, Department of Internal Medicine (DiMI), University of Genoa, IRCCS AOU San Martino-IST, 1600 Genoa, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Ballerini
authors.affiliation: Hematology Unit, Department of Internal Medicine (DiMI), University of Genoa, IRCCS AOU San Martino-IST, 1600 Genoa, Italy.
authors.forename: Marino
authors.initials: M
authors.lastname: Calvio
authors.affiliation: Hematology Unit, Department of Internal Medicine (DiMI), University of Genoa, IRCCS AOU San Martino-IST, 1600 Genoa, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Miglino
authors.affiliation: Hematology Unit, Department of Internal Medicine (DiMI), University of Genoa, IRCCS AOU San Martino-IST, 1600 Genoa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
authors.affiliation: Hematology Unit, Department of Internal Medicine (DiMI), University of Genoa, IRCCS AOU San Martino-IST, 1600 Genoa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Lemoli
authors.affiliation: Hematology Unit, Department of Internal Medicine (DiMI), University of Genoa, IRCCS AOU San Martino-IST, 1600 Genoa, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Cea
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D009101:Multiple Myeloma / Q000235:genetics*; D009154:Mutation / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm