Genomic patterns of progression in smoldering multiple myeloma

Abstract : We analyzed whole genomes of unique paired samples from smoldering multiple mye-loma (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 dea-minase 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [44 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01885513
Contributor : Elizabeth Bernardo <>
Submitted on : Tuesday, October 2, 2018 - 7:56:22 AM
Last modification on : Wednesday, August 7, 2019 - 12:18:06 PM
Long-term archiving on : Thursday, January 3, 2019 - 12:54:29 PM

File

BolliNatcomm2018Eq11.pdf
Publication funded by an institution

Identifiers

Collections

Citation

Niccolò Bolli, Francesco Maura, Stephane Minvielle, Dominik Gloznik, Raphael Szalat, et al.. Genomic patterns of progression in smoldering multiple myeloma. Nature Communications, Nature Publishing Group, 2018, 9 (1), pp.3363. ⟨10.1038/s41467-018-05058-y⟩. ⟨inserm-01885513⟩

Share

Metrics

Record views

106

Files downloads

122