What are the genetic abnormalities in monoclonal gammopathy of undetermined significance (MGUS)?

Updated: Sep 07, 2018
  • Author: Suzanne R Fanning, DO; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

Kyle et al reported that the cells in IgG and IgA MGUS arise from a mature, somatically mutated, postswitch plasma cell. About 50% of cases have evidence of translocation in the Ig heavy-chain region at 14q32. In contrast, IgM MGUS is described as arising from somatically mutated, postgerminal center B lymphocytes that have not undergone isotype class switching and therefore do not have the 14q32 translocation. These translocations are thought to be important in initiating and sustaining clonal proliferation. [4]

Several studies have confirmed that characteristic genetic abnormalities of multiple myeloma (MM) are present in patients with MGUS. [5, 6, 7] Gene-expression profiling has also led to a group with MGUS-like features. This group of patients had a lower complete remission rate, yet also had a lower-risk clinical course and superior survival. [8]

Nagoshi et al identified a possible secondary genetic change involving MGUS; they found transcriptional dysregulation of the deleted in colorectal carcinoma (DCC) gene in 25% of MGUS cases studied, and in 57% of MM. The DCC gene encodes a tumor suppressor that prevents cell growth; allele loss or decreased expression of DCC has been associated with the progression of solid tumors and hematologic malignancies. [9]


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