BMC Genomics | |
Chromosome-breakage genomic instability and chromothripsis in breast cancer | |
Research Article | |
Sheida Nabavi1  Ewa Przybytkowski2  Mark Basik3  Kathleen Klein4  Celia MT Greenwood5  Michael T Barrett6  Elizabeth Lenkiewicz6  | |
[1] Beth Israel Deaconess Medical Center & Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA;Department of Oncology, Lady Davis Institute for Medical Research, McGill University, 3755 Cote Ste-Catherine Road, H3T-1E2, Montreal, Quebec, Canada;Department of Oncology, Lady Davis Institute for Medical Research, McGill University, 3755 Cote Ste-Catherine Road, H3T-1E2, Montreal, Quebec, Canada;Department of Surgery, McGill University, Montreal, QC, Canada;Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada;Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada;Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada;Pharmaceutical Genomics Division, Translational Genomics Research Institute, Scottsdale, Arizona, USA; | |
关键词: Breast cancer; Genomic instability; Array CGH; Copy number alterations; Chromosomal breakpoints; Chromothripsis; Gene amplification; | |
DOI : 10.1186/1471-2164-15-579 | |
received in 2014-02-07, accepted in 2014-06-13, 发布年份 2014 | |
来源: Springer | |
【 摘 要 】
BackgroundChromosomal 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.ResultsWe 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.ConclusionsOur 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.
【 授权许可】
CC BY
© Przybytkowski et al.; licensee BioMed Central Ltd. 2014
【 预 览 】
Files | Size | Format | View |
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RO202311091448499ZK.pdf | 2285KB | download |
【 参考文献 】
- [1]
- [2]
- [3]
- [4]
- [5]
- [6]
- [7]
- [8]
- [9]
- [10]
- [11]
- [12]
- [13]
- [14]
- [15]
- [16]
- [17]
- [18]
- [19]
- [20]
- [21]
- [22]
- [23]
- [24]
- [25]
- [26]
- [27]
- [28]
- [29]
- [30]
- [31]
- [32]
- [33]