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33 patients with Monoclonal Gammopathy of Undetermined Significance (MGUS) had whole exome sequencing performed. Cells were sorted by FACSAria using CD138, CD19 and CD56 to obtain a pure abnormal plasma cell population. Generated somatic variants were compared to a previous study of 463 multiple myeloma patients.

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 molecular mechanism of malignant transformation. We have performed whole exome sequencing together with SNP array analysis in 33 flow-cytometry separated abnormal PC samples of MGUS patients to describe somatic gene mutations and chromosome changes at the genome-wide level. Non-synonymous mutations (NS-SNVs) and copy number alterations (CNAs) were present in 97.0% and in 63.6% of cases, respectively. Importantly, the number of somatic mutations was significantly lower in MGUS compared to MM (p<10-4) and we have identified 6 myeloma significantly mutated genes which are 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 primary lesion hypothesis. Data from this study showed MGUS is a genetically comprehensive disease, however overall genetic instability is significantly lower compared to MM.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001001901 Illumina HiSeq 2000 66
Publications Citations
The spectrum of somatic mutations in monoclonal gammopathy of undetermined significance indicates a less complex genomic landscape than that in multiple myeloma.
Haematologica 102: 2017 1617-1625
Genomic analysis of primary plasma cell leukemia reveals complex structural alterations and high-risk mutational patterns.
Blood Cancer J 10: 2020 70
Whole-genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities.
Nat Commun 12: 2021 1861
Characterizing the mutational landscape of MM and its precursor MGUS.
Am J Cancer Res 12: 2022 1919-1933
BDL-SP: A Bio-inspired DL model for the identification of altered Signaling Pathways in Multiple Myeloma using WES data.
Am J Cancer Res 13: 2023 1155-1187