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Updated: Jan 21, 2026
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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
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Mutational processes contributing to the development of multiple myeloma.
Phuc H Hoang1,2, Alex J Cornish1, Sara E Dobbins1
1Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Blood Cancer Journal
|August 8, 2019
Summary
This study reveals distinct mutational signatures in multiple myeloma (MM) development, linked to aging, DNA repair, and APOBEC activity. These signatures offer insights into MM subgroups and high-risk prediction.
Area of Science:
- Genomics
- Cancer Biology
- Molecular Oncology
Background:
- Multiple myeloma (MM) is a hematological malignancy with complex genetic underpinnings.
- Understanding the mutational landscape of MM is crucial for deciphering its tumorigenesis and identifying therapeutic targets.
Purpose of the Study:
- To investigate the mutational signatures in coding and non-coding regions of multiple myeloma.
- To identify distinct mutational processes and their association with MM subgroups and clinical outcomes.
Main Methods:
- Analysis of whole-exome and whole-genome sequencing data from 874 and 850 multiple myeloma patients, respectively, within the CoMMpass Study.
- Identification and characterization of single-nucleotide variant (SNV) and structural rearrangement mutational signatures.
- Correlation of mutational signatures with MM-associated translocations and cytogenetic subgroups.
Main Results:
- Distinct mutational signatures characterize coding and non-coding regions in MM.
- Identified signatures related to aging, DNA repair deficiency, and apolipoprotein B editing complex (APOBEC)/activation-induced deaminase activity.
- APOBEC signatures are associated with MAF translocations (t(14;16), t(14;20)), DNA repair deficiency with t(11;14) and t(4;14), and aging with hyperdiploidy.
- Mutational signatures, independent of APOBEC, predict high-risk MM and are distinct from established prognostic markers.
Conclusions:
- Mutational signatures provide a framework for understanding MM heterogeneity and evolution.
- Specific mutational processes are linked to distinct MM genetic subtypes.
- Non-APOBEC mutational signatures hold prognostic value for identifying high-risk multiple myeloma patients.
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