Mutational processes contributing to the development of multiple myeloma.
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Embargo End Date
ICR Authors
Authors
Hoang, PH
Cornish, AJ
Dobbins, SE
Kaiser, M
Houlston, RS
Cornish, AJ
Dobbins, SE
Kaiser, M
Houlston, RS
Document Type
Journal Article
Date
2019-08-06
Date Accepted
2019-05-08
Abstract
To gain insight into multiple myeloma (MM) tumorigenesis, we analyzed the mutational signatures in 874 whole-exome and 850 whole-genome data from the CoMMpass Study. We identified that coding and non-coding regions are differentially dominated by distinct single-nucleotide variant (SNV) mutational signatures, as well as five de novo structural rearrangement signatures. Mutational signatures reflective of different principle mutational processes-aging, defective DNA repair, and apolipoprotein B editing complex (APOBEC)/activation-induced deaminase activity-characterize MM. These mutational signatures show evidence of subgroup specificity-APOBEC-attributed signatures associated with MAF translocation t(14;16) and t(14;20) MM; potentially DNA repair deficiency with t(11;14) and t(4;14); and aging with hyperdiploidy. Mutational signatures beyond that associated with APOBEC are independent of established prognostic markers and appear to have relevance to predicting high-risk MM.
Citation
Blood cancer journal, 2019, 9 (8), pp. 60 - ?
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
2044-5385
eISSN
2044-5385
Collections
Research Team
Cancer Genomics
Molecular & Population Genetics
Myeloma Group
Molecular & Population Genetics
Myeloma Group