Open Access Research article

Chromosome-breakage genomic instability and chromothripsis in breast cancer

Ewa Przybytkowski1*, Elizabeth Lenkiewicz3, Michael T Barrett3, Kathleen Klein4, Sheida Nabavi5, Celia MT Greenwood46 and Mark Basik12

Author Affiliations

1 Department of Oncology, Lady Davis Institute for Medical Research, McGill University, 3755 Cote Ste-Catherine Road, Montreal, Quebec H3T-1E2, Canada

2 Department of Surgery, McGill University, Montreal, QC, Canada

3 Pharmaceutical Genomics Division, Translational Genomics Research Institute, Scottsdale, Arizona, USA

4 Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada

5 Beth Israel Deaconess Medical Center & Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA

6 Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada

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BMC Genomics 2014, 15:579  doi:10.1186/1471-2164-15-579

Published: 9 July 2014



Chromosomal breakage followed by faulty DNA repair leads to gene amplifications and deletions in cancers. However, the mere assessment of the extent of genomic changes, amplifications and deletions may reduce the complexity of genomic data observed by array comparative genomic hybridization (array CGH). We present here a novel approach to array CGH data analysis, which focuses on putative breakpoints responsible for rearrangements within the genome.


We performed array comparative genomic hybridization in 29 primary tumors from high risk patients with breast cancer. The specimens were flow sorted according to ploidy to increase tumor cell purity prior to array CGH. We describe the number of chromosomal breaks as well as the patterns of breaks on individual chromosomes in each tumor. There were differences in chromosomal breakage patterns between the 3 clinical subtypes of breast cancers, although the highest density of breaks occurred at chromosome 17 in all subtypes, suggesting a particular proclivity of this chromosome for breaks. We also observed chromothripsis affecting various chromosomes in 41% of high risk breast cancers.


Our results provide a new insight into the genomic complexity of breast cancer. Genomic instability dependent on chromosomal breakage events is not stochastic, targeting some chromosomes clearly more than others. We report a much higher percentage of chromothripsis than described previously in other cancers and this suggests that massive genomic rearrangements occurring in a single catastrophic event may shape many breast cancer genomes.

Breast cancer; Genomic instability; Array CGH; Copy number alterations; Chromosomal breakpoints; Chromothripsis; Gene amplification