Acquired genomic copy number aberrations in CLL

Adv Exp Med Biol. 2013;792:47-86. doi: 10.1007/978-1-4614-8051-8_3.


Approximately 80 % of chronic lymphocytic leukemia (CLL) carries somatically acquired genomic copy number aberrations (aCNAs). These include gains of entire chromosomes (trisomy 12) and recurrent genomic losses, including interstitial deletions of various lengths at 13q14, 11q, and of more uniform length at 17p. In addition, approximately 10-15 second-tier aCNAs, with frequencies of 1-5 %, have been identified. In this chapter, we will discuss the biology and clinical significance of these CLL-associated aCNAs in detail and also discuss generic aspects of aCNAs relevant to all cancer cells. The hypothesis is advanced that most if not all aCNAs in CLL deregulate multiple target genes as a consequence of aCNA-associated gene mutations and through stable deregulation of gene expression. The concept of elevated genomic complexity (multiple aCNAs per CLL case) is reinforced as one of the strongest biological traits associated with aggressive CLL with short survival. Further, all inherited polymorphic copy number variations as detected through SNP 6.0 array profiling of T-cell-derived DNA of 255 CLL patients are listed to allow the reader a more critical appraisal of the somatic status of CLL-associated aCNAs as reported in the literature. Finally, given that aCNAs and gene mutations coexist in many CLL cells, we stress the importance of understanding in detail the relative biological and clinical roles each mutation type serves in individual CLL patients; this is a research area in need of more in-depth investigation.

Publication types

  • Review

MeSH terms

  • DNA Copy Number Variations*
  • Humans
  • Karyotyping
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Translocation, Genetic