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Genomewide profiling of copy-number alteration in monoclonal gammopathy of undetermined significance
A. Mikulasova, J. Smetana, M. Wayhelova, H. Janyskova, V. Sandecka, Z. Kufova, M. Almasi, J. Jarkovsky, E. Gregora, P. Kessler, M. Wrobel, BA. Walker, CP. Wardell, GJ. Morgan, R. Hajek, P. Kuglik,
Language English Country England, Great Britain
Document type Journal Article
Grant support
NT13492
MZ0
CEP Register
PubMed
27157252
DOI
10.1111/ejh.12774
Knihovny.cz E-resources
- MeSH
- Genome-Wide Association Study * MeSH
- Chromosome Aberrations MeSH
- Genomics * methods MeSH
- Humans MeSH
- Multiple Myeloma diagnosis genetics MeSH
- Monoclonal Gammopathy of Undetermined Significance diagnosis genetics MeSH
- Genomic Instability MeSH
- Disease Progression MeSH
- Comparative Genomic Hybridization MeSH
- DNA Copy Number Variations * MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
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.
Department of Clinical Hematology University Hospital Brno Brno Czech Republic
Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic
Department of Hematology and Transfusion General Hospital Pelhrimov Czech Republic
Department of Internal Medicine Hematology and Oncology University Hospital Brno Brno Czech Republic
Department of Oncology Hospital Novy Jicin Novy Jicin Czech Republic
Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University Brno Czech Republic
Myeloma Institute University of Arkansas for Medical Sciences Little Rock AR USA
References provided by Crossref.org
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