Mutational processes contributing to the development of multiple myeloma

Blood Cancer Journal
Phuc H HoangR S Houlston

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.

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Citations

Feb 7, 2020·International Journal of Hematology·Yusuke Furukawa, Jiro Kikuchi
Jul 21, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mehmet Kemal SamurNikhil C Munshi
May 3, 2020·Blood Cancer Journal·Phuc H HoangRichard S Houlston
Dec 6, 2020·Genes, Chromosomes & Cancer·Maurus LocherNormann Steiner
Aug 8, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Francesco MauraGareth J Morgan
Jan 27, 2021·Cancers·Timon A BloedjesJeroen E J Guikema
Oct 16, 2020·Blood Cancer Journal·Phuc H HoangRichard S Houlston
May 1, 2021·International Journal of Molecular Sciences·Ryszard OlinskiHans Einar Krokan
Aug 29, 2021·Nature Communications·Kylee H MaclachlanFrancesco Maura
Oct 10, 2021·Blood Cancer Journal·Srikanth TalluriNikhil C Munshi

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Datasets Mentioned

BETA
GM12813
GM12801

Methods Mentioned

BETA
Genetic Profile
exome sequencing
RNAseq

Software Mentioned

ENCODE
Palimpsest
CRG GEM mappability tool
survminer R package
CoMMpass
ConsensusClusterPlus R package
MuTect
Strelka
HTseq
Ensembl

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