The clonal evolution during long-term clinical course of multiple myeloma

Int J Hematol. 2021 Feb;113(2):279-284. doi: 10.1007/s12185-020-02979-7. Epub 2020 Aug 30.

Abstract

Somatic gene mutations related to acceleration disease and clonal evolution in multiple myeloma strongly influence severe clinical outcomes. In this study, we traced the transition of somatic mutations during the clinical course of myeloma patients over a long-term follow-up period (8.5 year average). Seven myeloma cases treated with immuno-chemotherapy at our institution were analyzed with clinical courses and the results of FISH and G-band analyses. Furthermore, the target sequences in regard to 121 genes, related to driver mutations or acceleration of disease in myeloma, were performed using bone marrow myeloma samples by next-generation sequencing, Ion Proton™ System. We detected a relationship between an increase in the dominant mutated gene (e.g., TP53, DIS3, FAM46C, KDM6B, and EGR1) and poor prognosis. In particular, clonal escalation of the TP53 mutation could not be overcome by any treatment. The selection of a combination treatment conducted in conjunction with the monitoring of gene mutations is appropriate for long-term survival. Our data demonstrate that long-term follow-up of somatic gene mutations during the clinical course of myeloma is helpful in the development of an effective treatment strategy.

Keywords: Clonal evolution; Gene mutation; Multiple myeloma; Resistance for therapy; Somatic gene mutation analysis.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Biomarkers, Tumor
  • Cell Transformation, Neoplastic
  • Clonal Evolution* / genetics
  • Combined Modality Therapy / adverse effects
  • Combined Modality Therapy / methods
  • Computational Biology / methods
  • Databases, Genetic
  • Disease Progression
  • Disease Susceptibility*
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Genetic Variation
  • Humans
  • Middle Aged
  • Multiple Myeloma / diagnosis*
  • Multiple Myeloma / etiology*
  • Multiple Myeloma / mortality
  • Multiple Myeloma / therapy
  • Mutation
  • Neoplasm Staging
  • Treatment Outcome

Substances

  • Biomarkers, Tumor