Genome-wide association study of monoclonal gammopathy of unknown significance (MGUS): comparison with multiple myeloma
Abstrakt
In summary, the present GWAS on MGUS appears to be capable of delineating distinctions between MGUS and MM germlines. Associations with the PROX1, SFMBT, RAD51B, and CSNK1G1 loci were only found for MGUS, which may suggest that they are less important in the course of progression to MM.
These genes have known functions in plasma cells and/or carcinogenesis, including homeobox transcription factor (PROX1) interacting with GATA2, chromatin remodeling through histone modification (SFMBT), double-stranded DNA repair (RAD51B), and cell cycle checkpoint arrest, DNA repair, and Wnt signaling (CSNK1G1). These are the functions that have been proposed to the SNPs identified in MM (chromatin remodeling, B-cell development, and cell cycle/genomic stability); additionally, apoptosis/autophagy pathways were suggested for MM for which we did not find evidence in MGUS [3].
The association with TNFRSF13 was stronger in MGUS compared to MM but the reverse was the case for the SNP forming the IRF4-binding site. PREX1 and TOM1 associations were only found in MM.
If such distinctions can be verified in independent studies on MGUS they advance molecular understanding of the progression process, of the related prognostic markers and of the possible targets for intervention.