Genomics

Dataset Information

44

Genome-wide 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 genome-wide 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. Overall design: A total of 90 patients with monoclonal gammopathy of undetermined significance and 33 patients with multiple myeloma were included in this study. An abnormal plasma cell population (CD138+CD19-CD56+/-) was isolated from all MGUS patients and one MM patient. A normal plasma cell population (CD138+CD19+CD56-) was also isolated from 13 out of 90 MGUS patients. In the remaining 32 MM samples, CD138+ plasma cells were obtained. Promega Human Genomic DNA or Agilent Human Reference DNA was used as reference DNA.

INSTRUMENT(S): Agilent-021924 SurePrint G3 Human CGH Microarray 8x60K (Feature Number version)

SUBMITTER: Aneta Mikulasova  

PROVIDER: GSE77975 | GEO | 2016-02-18

SECONDARY ACCESSION(S): PRJNA312349

REPOSITORIES: GEO

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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 i  ...[more]

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