Genomewide profiling of copy‐number alteration in monoclonal gammopathy of undetermined significance

Abstract

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 ( CNA s) in 90 MGUS and 33 MM patients using high‐density DNA microarrays. We identified CNA s in a smaller proportion of MGUS (65.6%) than in MM (100.0%, P = 1.31 × 10 −5 ) and showed median number of CNA s 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 CNA s 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.