Mechanisms and Clinical Applications of Genome Instability in Multiple Myeloma

Biomed Res Int. 2015:2015:943096. doi: 10.1155/2015/943096. Epub 2015 Oct 22.

Abstract

Ongoing genomic instability represents a hallmark of multiple myeloma (MM) cells, which manifests largely as whole chromosome- or translocation-based aneuploidy. Importantly, although it supports tumorigenesis, progression and, response to treatment in MM patients, it remains one of the least understood components of malignant transformation in terms of molecular basis. Therefore these aspects make the comprehension of genomic instability a pioneering strategy for novel therapeutic and clinical speculations to use in the management of MM patients. Here we will review mechanisms mediating genomic instability in MM cells with an emphasis placed on pathogenic mutations affecting DNA recombination, replication and repair, telomere function and mitotic regulation of spindle attachment, centrosome function, and chromosomal segregation. We will discuss the mechanisms by which genetic aberrations give rise to multiple pathogenic events required for myelomagenesis and conclude with a discussion of the clinical applications of these findings in MM patients.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA Damage / genetics
  • DNA, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genes, Neoplasm / genetics*
  • Genome, Human / genetics*
  • Genomic Instability / genetics*
  • Humans
  • Models, Genetic
  • Multiple Myeloma / genetics*
  • Mutation / genetics

Substances

  • DNA, Neoplasm