Timing the initiation of multiple myeloma Journal Article

   


Authors: Rustad, E. H.; Yellapantula, V.; Leongamornlert, D.; Bolli, N.; Ledergor, G.; Nadeu, F.; Angelopoulos, N.; Dawson, K. J.; Mitchell, T. J.; Osborne, R. J.; Ziccheddu, B.; Carniti, C.; Montefusco, V.; Corradini, P.; Anderson, K. C.; Moreau, P.; Papaemmanuil, E.; Alexandrov, L. B.; Puente, X. S.; Campo, E.; Siebert, R.; Avet-Loiseau, H.; Landgren, O.; Munshi, N.; Campbell, P. J.; Maura, F.
Article Title: Timing the initiation of multiple myeloma
Abstract: The evolution and progression of multiple myeloma and its precursors over time is poorly understood. Here, we investigate the landscape and timing of mutational processes shaping multiple myeloma evolution in a large cohort of 89 whole genomes and 973 exomes. We identify eight processes, including a mutational signature caused by exposure to melphalan. Reconstructing the chronological activity of each mutational signature, we estimate that the initial transformation of a germinal center B-cell usually occurred during the first 2nd-3rd decades of life. We define four main patterns of activation-induced deaminase (AID) and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) mutagenesis over time, including a subset of patients with evidence of prolonged AID activity during the pre-malignant phase, indicating antigen-responsiveness and germinal center reentry. Our findings provide a framework to study the etiology of multiple myeloma and explore strategies for prevention and early detection. © 2020, The Author(s).
Keywords: cancer chemotherapy; controlled study; human tissue; unclassified drug; gene mutation; major clinical study; sequence analysis; mutation; cancer recurrence; cancer growth; phenotype; multiple myeloma; gene expression; protein; genetic variability; evolution; melphalan; autologous stem cell transplantation; genetic transcription; peptide; mutational analysis; time; age; b lymphocyte; carcinogenesis; germinal center; activation induced cytidine deaminase; immunoglobulin heavy chain; antigen; cell transformation; heterozygosity; genome; plasma; catalyst; transformation; cell; etiology; clinical trial (topic); copy number variation; exposure; nucleic acid base substitution; mutagenicity; complementarity determining region; human; article; whole genome sequencing; whole exome sequencing; apolipoprotein b mrna editing enzyme catalytic polypeptide like; molecular clock; single cell rna seq; apolipoprotein b mrna editing enzyme catalytic subunit 3a; apolipoprotein b mrna editing enzyme catalytic subunit 3b; transcription factor mafa; transcription factor mafb
Journal Title: Nature Communications
Volume: 11
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2020-04-21
Start Page: 1917
Language: English
DOI: 10.1038/s41467-020-15740-9
PUBMED: 32317634
PROVIDER: scopus
PMCID: PMC7174344
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85083766939&doi=10.1038%2fs41467-020-15740-9&partnerID=40&md5=a593aa07d3032c8ffe98399bae2caae5
Notes: Article -- Export Date: 1 June 2020 -- Source: Scopus
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MSK Authors
  1. Carl Ola Landgren
    336 Landgren
  2. Elli Papaemmanuil
    206 Papaemmanuil
  3. Venkata D Yellapantula
    51 Yellapantula
  4. Even Holth Rustad
    43 Rustad
  5. Francesco Maura
    57 Maura
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