Chromothripsis identifies a rare and aggressive entity among newly diagnosed multiple myeloma patients

Blood. 2011 Jul 21;118(3):675-8. doi: 10.1182/blood-2011-03-344069. Epub 2011 May 31.


Multiple myeloma (MM) develops from a premalignant plasma cell proliferative disorder, and with time can progress to a more aggressive disease in extramedullary locations. The gradually clinical evolution is supported by clonal expansion of cells that acquire genetic lesions over years. This model of cancer evolution based on ongoing genomic instability mechanism may apply to development of most MM cases. However, in a small fraction of newly diagnosed MM who relapse quickly and finally die within 2 years, the gradual model appears to be untenable. Analysis of high resolution copy number profiles obtained using single nucleotide polymorphism array data from 764 newly diagnosed MM identified large numbers of genomic rearrangements with the hallmarks of chromothripsis in 1.3% of samples. Moreover, this catastrophic event confers a poor outcome. Because chromothripsis appears to occur in a single crisis, our results suggest that high-risk MM patients use this novel way of cancer evolution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Chromosome Breakage
  • Gene Dosage / genetics
  • Gene Rearrangement / genetics*
  • Genomic Instability / genetics*
  • Genomics
  • Humans
  • Middle Aged
  • Molecular Sequence Data
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / mortality*
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors

Associated data

  • GENBANK/GSE27560