Somatic mutation spectrum in monoclonal gammopathy of undetermined significance indicates a simpler genomic landscape compared to multiple myeloma
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ABSTRACT: 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.
ORGANISM(S): Homo sapiens
PROVIDER: GSE77979 | GEO | 2016/02/18
SECONDARY ACCESSION(S): PRJNA312372
REPOSITORIES: GEO
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