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Title: Somatic mutation spectrum in monoclonal gammopathy of undetermined significance indicates a simpler genomic landscape compared to multiple myeloma      
keywords:
Variation
ID:
PRJNA312372
description:
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma (MM) with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS genes mutations, little is known about the molecular mechanism of malignant transformation. We have performed whole-exome sequencing together with CGH+SNP array analysis in 33 flow-cytometry separated abnormal plasma cell samples from MGUS patients to describe somatic gene mutations and chromosome changes at the genome-wide level. Non-synonymous mutations and copy-number alterations were present in 97.0% and in 60.6% of cases, respectively. Importantly, the number of somatic mutations was significantly lower in MGUS compared to MM (p<10-4) and we have identified six genes that are significantly mutated in MM (KRAS, NRAS, DIS3, HIST1H1E, EGR1 and LTB) in the MGUS dataset. We also found a positive correlation with increasing chromosome changes and somatic mutations. IGH translocations were present in 27.3% of cases comprising t(4;14), t(11;14), t(14;16) or t(14;20) and were in a similar frequency to MM, which corresponded with the primary lesion hypothesis. Data from this study showed MGUS is a genetically comprehensive disease, however, overall genetic instability is significantly lower compared to MM. Overall design: Overall, 33 MGUS patients were included in this study. Genomic DNA was isolated from flow-cytometry separated abnormal plasma cells and analysed by CGH+SNP arrays to describe somatic gene mutations and chromosome changes at genome-wide level. Agilent Human Reference DNA was used as reference DNA.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA312372
authentication:
none
authorization:
none
name:
Homo sapiens
ncbiID:
ncbitax:9606
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject