title: Genomewide profiling of copy-number alteration in monoclonal gammopathy of undetermined significance.
abstract: Monoclonal gammopathy of undetermined significance (MGUS) is a benign condition with an approximate 1% annual risk of symptomatic plasma cell disorder development, mostly to multiple myeloma (MM). We performed genomewide screening of copy-number alterations (CNAs) in 90 MGUS and 33 MM patients using high-density DNA microarrays. We identified CNAs in a smaller proportion of MGUS (65.6%) than in MM (100.0%, P = 1.31 × 10-5) and showed median number of CNAs is lower in MGUS (3, range 0-22) than in MM (13, range 4-38, P = 1.82 × 10-10). In the MGUS cohort, the most frequent losses were located at 1p (5.6%), 6q (6.7%), 13q (30.0%), 14q (14.4%), 16q (8.9%), 21q (5.6%), and gains at 1q (23.3%), 2p (6.7%), 6p (13.3%), and Xq (7.8%). Hyperdiploidy was detected in 38.9% of MGUS cases, and the most frequent whole chromosome gains were 3 (25.6%), 5 (23.3%), 9 (37.8%), 15 (23.3%), and 19 (32.2%). We also identified CNAs such as 1p, 6q, 8p, 12p, 13q, 16q losses, 1q gain and hypodiploidy, which are potentially associated with an adverse prognosis in MGUS. In summary, we showed that MGUS is similar to MM in that it is a genetically heterogeneous disorder, but overall cytogenetic instability is lower than in MM, which confirms that genetic abnormalities play important role in monoclonal gammopathies.
authors.affiliation: Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.|Department of Medical Genetics, University Hospital Brno, Brno, Czech Republic.|Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
authors.forename: Aneta
authors.initials: A
authors.lastname: Mikulasova
authors.affiliation: Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.|Department of Medical Genetics, University Hospital Brno, Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Smetana
authors.affiliation: Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.|Department of Medical Genetics, University Hospital Brno, Brno, Czech Republic.
authors.forename: Marketa
authors.initials: M
authors.lastname: Wayhelova
authors.affiliation: Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
authors.forename: Helena
authors.initials: H
authors.lastname: Janyskova
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
authors.forename: Viera
authors.initials: V
authors.lastname: Sandecka
authors.affiliation: Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.|Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Kufova
authors.affiliation: Department of Clinical Hematology, University Hospital Brno, Brno, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Almasi
authors.affiliation: Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Jarkovsky
authors.affiliation: Department of Internal Medicine and Hematology, University Hospital Kralovske Vinohrady, Prague, Czech Republic.
authors.forename: Evzen
authors.initials: E
authors.lastname: Gregora
authors.affiliation: Department of Hematology and Transfusion, General Hospital, Pelhrimov, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Kessler
authors.affiliation: Department of Oncology, Hospital Novy Jicin, Novy Jicin, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Wrobel
authors.affiliation: Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Walker
authors.affiliation: Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.|Laboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Wardell
authors.affiliation: Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
authors.affiliation: Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.|Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic.
authors.forename: Roman
authors.initials: R
authors.lastname: Hajek
authors.affiliation: Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.|Department of Medical Genetics, University Hospital Brno, Brno, Czech Republic.|Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Kuglik
mesh_terms: D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D018450:Disease Progression; D005260:Female; D055106:Genome-Wide Association Study; D042822:Genomic Instability; D023281:Genomics / Q000379:methods; D006801:Humans; D008297:Male; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000175:diagnosis / Q000235:genetics*; D009101:Multiple Myeloma / Q000175:diagnosis / Q000235:genetics
keywords: DNA copy-number changes; DNA microarrays; monoclonal gammopathies; prognosis