Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma
Open accessAbstract
Key Points: Using the largest set of patients with newly diagnosed myeloma, we identified 63 mutated driver genes. We identified oncogenic dependencies, particularly relating to primary translocations, indicating a nonrandom accumulation of genetic hits.
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Multiple myeloma and MGUS/SMM have two key groups of initiating events: immunoglobulin (IGH) translocations and hyperdiploidy (HY).
“Historically, MM and MGUS/SMM have two key groups of initiating events: immunoglobulin (IGH) translocations and hyperdiploid (HY).9,54-59”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [58]
The Introduction (page not provided) says MM can broadly be divided into cases with primary immunoglobulin translocations and cases that are hyperdiploid. The Discussion (page not provided) describes primary events as initiating genetic progression. These passages support the claim for MM, but our copy does not establish the same two groups of initiating events for MGUS or SMM. (LLM, conf=0.86)
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“11-13 We have shown this previously with translocation groups and their partner genes, such as t(11;14) and mutation of CCND1.”
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Self-citation
- Authors
- Walker, B. A., Mavrommatis, K., Wardell, C. P., Ashby, T. C., Bauer, M., Davies, F. E., Rosenthal, A., Wang, H., Qu, P., Hoering, A., Samur, M., Towfic, F., Ortiz, M., Flynt, E., Yu, Z., Yang, Z., Rozelle, D., Obenauer, J., Trotter, M., Auclair, D., Keats, J., Bolli, N., Fulciniti, M., Szalat, R., Moreau, P., Durie, B., Stewart, A. K., Goldschmidt, H., Raab, M. S., Einsele, H., Sonneveld, P., San Miguel, J., Lonial, S., Jackson, G. H., Anderson, K. C., Avet-Loiseau, H., Munshi, N., Thakurta, A., & Morgan, G. J.
- Affiliations
- University of Arkansas for Medical Sciences (US)
- Celgene Corporation, San Francisco, CA;
- Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR;
- Cancer Research And Biostatistics (US)
- Harvard University (US)
- Celgene (United States) (US)
- Celgene Institute of Translational Research Europe, Sevilla, Spain;
- Rancho BioSciences (United States) (US)
- Multiple Myeloma Research Foundation (US)
- Translational Genomics Research Institute (US)
- Department of Oncology, University of Milan, Milan, Italy;
- Université de Nantes (FR)
- Cedars-Sinai Medical Center (US)
- Mayo Clinic in Arizona (US)
- University Hospital Heidelberg (DE)
- German Cancer Research Center (DE)
- University of Würzburg (DE)
- Erasmus MC Cancer Institute (NL)
- Centro Investigacion Medica Aplicada, Clinica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra, Centro de Investigación Biomédica en Red de Oncología, Pamplona, Spain;
- Emory University (US)
- Newcastle University (GB)
- Centre de Recherche en Cancérologie de Toulouse Institut National de la Santé et de la Recherche Médicale U1037, Toulouse, France; and
- Corresponding author
- Walker, Brian A.
- Mavrommatis, Konstantinos
- Wardell, Christopher P.
- Munshi, Nikhil
- Thakurta, Anjan
- Morgan, Gareth J.
- ORCID
- Walker, Brian A.
- Mavrommatis, Konstantinos
- Wardell, Christopher P.
- Bauer, Michael
- Davies, Faith E.
- Rosenthal, Adam
- Wang, Hongwei
- Qu, Pingping
- Hoering, Antje
- Samur, Mehmet
- Towfic, Fadi
- Flynt, Erin
- Rozelle, Dan
- Obenauer, John
- Trotter, Matthew
- Auclair, Daniel
- Keats, Jonathan
- Fulciniti, Mariateresa
- Szalat, Raphael
- Moreau, Philippe
- Durie, Brian
- Goldschmidt, Hartmut
- Raab, Marc S.
- Einsele, Hermann
- Sonneveld, Pieter
- Lonial, Sagar
- Jackson, Graham H.
- Anderson, Kenneth C.
- Munshi, Nikhil
- Thakurta, Anjan
- Morgan, Gareth J.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2018-08-09
- Volume
- 132
- Issue
- 6
- Pages
- 587-597
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC6097138
- OpenAlex
- W2805293188
- Cited by
- 475
- References
- 5
- Citations by year
- 2026: 31 · 2025: 42 · 2024: 55 · 2023: 66 · 2022: 86 · 2021: 63 · 2020: 68 · 2019: 52 · 2018: 8
- FWCI
- 34.24
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-09-27)
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Celgene
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Keywords
- multiple myeloma, chromosomal translocation, genomic landscape, tumor evolution, treatment resistance
- MeSH terms
- Exome Sequencing, Clone Cells, DNA Mutational Analysis, DNA, Neoplasm, Humans, Multiple Myeloma, Mutation, Oncogenes, Prognosis, Translocation, Genetic, Gene Expression Regulation, Neoplastic, Mutagenesis, Treatment Outcome, Gene Dosage, Loss of Heterozygosity, Genomics, Genomic Instability, Genome-Wide Association Study, Datasets as Topic
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