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The spectrum of somatic mutations in monoclonal gammopathy of undetermined significance indicates a less complex genomic landscape than that in multiple myeloma

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Mikulasova, Aneta, Wardell, Christopher P., Murison, Alexander, Boyle, Eileen M., Jackson, Graham H., Smetana, Jan, Kufova, Zuzana, Pour, Ludek +9 more·2017·Haematologica
DOI 10.3324/haematol.2017.163766PMC PMC5685224
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Abstract

Monoclonal gammopathy of undetermined significance is a pre-malignant precursor of multiple myeloma 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 gene mutations, little is known about the molecular mechanism of malignant transformation. We performed whole exome sequencing together with comparative genomic hybridization plus single nucleotide polymorphism array analysis in 33 flow-cytometry-separated abnormal plasma cell samples from patients with monoclonal gammopathy of undetermined significance 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 monoclonal gammopathy of undetermined significance than in myeloma (P

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  • Neoplastic transformation occurs early in time.

    “suggesting that the neoplastic transformation occurs early in time.9,11,79,80,85”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [80]

    The Abstract and Discussion (page unavailable) show that myeloma-associated genetic changes are already present in MGUS, a premalignant precursor, supporting an early stage of genomic change. They do not establish that neoplastic transformation itself occurs early in time; the Discussion distinguishes changes present in MGUS from those likely involved in progression. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Patterns of genomic complexity and neoplastic transformation can already be observed in some MGUS and low-risk SMM cases several years before progression.

    “Interestingly, these patterns of genomic complexity and neoplastic transformation can already be observed in some MGUS and low-risk SMM cases several years before progression, suggesting that the neoplastic transformation occurs early in time.9,11,79,80,85”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [80]

    The Results (risk stratification; page unavailable) show that some MGUS cases had chromosomal abnormalities, and the Discussion describes early genetic heterogeneity in MGUS. The paper does not establish that these patterns occurred in low-risk SMM cases or several years before progression. Its Discussion says that following cases from MGUS through SMM to MM would provide further insight, and notes that two MGUS patients with RAS mutations had not progressed after 50 and 67 months. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • RAS mutations, MYC translocations, APOBEC mutagenesis, and patterns of genomic complexity are the most commonly reported alterations in progressing multiple myeloma.

    “Among these, RAS mutations, MYC translocations, APOBEC mutagenesis, and patterns of genomic complexity are the most commonly reported.8,9,11,69,76-83,84”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [80]

    The Discussion (page unavailable) identifies RAS mutations and MYC translocations as likely candidates in disease progression. The Results (page unavailable) report no APOBEC signature in the MGUS cohort and suggest it may be acquired later in MM; the paper also describes increasing genomic changes. It does not establish that these four are the most commonly reported alterations in progressing multiple myeloma. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Authors
Mikulasova, A., Wardell, C. P., Murison, A., Boyle, E. M., Jackson, G. H., Smetana, J., Kufova, Z., Pour, L., Sandecka, V., Almasi, M., Vsianska, P., Gregora, E., Kuglik, P., Hajek, R., Davies, F. E., Morgan, G. J., & Walker, B. A.
Affiliations
  • University of Arkansas for Medical Sciences (US)
  • Institute of Cancer Research (GB)
  • Newcastle University (GB)
  • Masaryk University (CZ)
Corresponding author
Walker, Brian A.
ORCID
Venue
Haematologica
Publisher
Ferrata Storti Foundation (Haematologica)
Published
2017-05-26
Volume
102
Issue
9
Pages
1617-1625
ISSN
  • 0390-6078 (ISSN-L)
  • 1592-8721
DOI
10.3324/haematol.2017.163766
PMC
PMC5685224
OpenAlex
W2619843656
Cited by
101
References
4
Citations by year
2026: 4 · 2025: 12 · 2024: 12 · 2023: 15 · 2022: 11 · 2021: 12 · 2020: 14 · 2019: 10 · 2018: 9 · 2017: 2
FWCI
7.38
Type
journal article
Language
en
Open access
Locations
  • Haematologica (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Newcastle University ePrints (Newcastle Univesity) (cc-by-nc)
Funders
  • Cancer Research UK
  • National Cancer Institute (P01CA055819)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
Keywords
monoclonal gammopathy of undetermined significance, multiple myeloma, somatic mutations, copy number alterations, malignant transformation, plasma cells, genomic landscape, IGH translocation, RB1 deletion, 1q gain, hyperdiploidy, RAS mutations, progression risk
MeSH terms
Chromosomes, Human, Female, Flow Cytometry, Humans, Male, Monoclonal Gammopathy of Undetermined Significance, Multiple Myeloma, Neoplasm Proteins, Translocation, Genetic

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