Genomic patterns of progression in smoldering multiple myeloma

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 AlexandrovDavid C Wedge, Herve Avet-Loiseau, Peter Campbell, Nikhil Munshi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3363
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - Aug 22 2018

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Keywords

  • Aged
  • Databases, Genetic
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genomics
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma/genetics
  • Mutation/genetics
  • Risk Factors
  • Smoldering Multiple Myeloma/genetics

Cite this

Bolli, N., Maura, F., Minvielle, S., Gloznik, D., Szalat, R., Fullam, A., Martincorena, I., Dawson, K. J., Samur, M. K., Zamora, J., Tarpey, P., Davies, H., Fulciniti, M., Shammas, M. A., Tai, Y. T., Magrangeas, F., Moreau, P., Corradini, P., Anderson, K., ... Munshi, N. (2018). Genomic patterns of progression in smoldering multiple myeloma. Nature Communications, 9(1), 3363. https://doi.org/10.1038/s41467-018-05058-y