Year: 2018
Type: article
Study design: Observational Study
Abstract: We analyzed whole genomes of unique paired samples from smoldering multiple myeloma (SMM) patients progressing to multiple myeloma (MM). We report that the genomic landscape, including mutational profile and structural rearrangements at the smoldering stage is very similar to MM. Paired sample analysis shows two different patterns of progression: a "static progression model", where the subclonal architecture is retained as the disease progressed to MM suggesting that progression solely reflects the time needed to accumulate a sufficient disease burden; and a "spontaneous evolution model", where a change in the subclonal composition is observed. We also observe that activation-induced cytidine deaminase plays a major role in shaping the mutational landscape of early subclinical phases, while progression is driven by APOBEC cytidine deaminases. These results provide a unique insight into myelomagenesis with potential implications for the definition of smoldering disease and timing of treatment initiation.
Source: Nature Communications
Authors: Niccolò Bolli, Francesco Maura, Stephane Minvielle, Dominik Gloznik, Raphael Szalat, Anthony Fullam, Inigo Martincorena, Kevin J. Dawson, Mehmet Kemal Samur, Jorge Zamora, Patrick Tarpey, Helen Davies, Mariateresa Fulciniti, Masood A. Shammas, Yu Tzu Tai, Florence Magrangeas, Philippe Moreau, Paolo Corradini, Kenneth Anderson, Ludmil Alexandrov, David C. Wedge, Herve Avet-Loiseau, Peter Campbell, Nikhil Munshi
Institutions: University of Milan, Wellcome Sanger Institute, Fondazione IRCCS Istituto Nazionale dei Tumori, Centre National de la Recherche Scientifique, Inserm, Centre Hospitalier Universitaire de Nantes, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers, Université de Nantes, Université d'Angers, Nantes Université, Harvard University, Dana-Farber Cancer Institute, University of California San Diego, Moores Cancer Center, University of Oxford, Institut universitaire du cancer de Toulouse Oncopole, VA Boston Healthcare System, Dana-Farber/Harvard Cancer Center
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Veterans Affairs, Leukemia and Lymphoma Society, Cancer Research UK, Associazione Italiana per la Ricerca sul Cancro, Associazione Italiana Contro le Leucemie-Linfomi e Mieloma, Società Italiana di Ematologia Sperimentale, National Institutes of Health, National Cancer Institute
OpenAlex ID: W2885104676