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Chromosome translocations in breast cancer
Breast Cancer Research volume 10, Article number: P6 (2008)
Genome rearrangement is a major mechanism of gene alteration in cancer. Chromosome translocations and inversions can result in gene fusion, promoter insertion or gene inactivation. In the past it has been assumed that such rearrangements are not significant players in the common epithelial cancers, as they are in leukaemias and sarcomas. However, this view is now being challenged. In particular, Tomlins and colleagues found that around 70% of prostate cancers have translocations or inversions of the ETS family of transcription factors . In breast cancer, we have shown that the NRG1/heregulin gene is translocated in 6% of primary cases  and Soda and colleagues described fusions of ALK in 7% of lung cancers .
Methods and results
We present a comprehensive analysis by array painting of the chromosome translocations of breast cancer cell lines HCC1806, HCC1187 and ZR-75-30. In array painting, chromosomes are isolated by flow cytometry, amplified and hybridized to DNA microarrays . A total of 200 breakpoints were identified and all were mapped to 1 Mb resolution on BAC arrays, then 40 selected breakpoints, including all balanced breakpoints, were further mapped on tiling-path BAC arrays or to around 2 kb resolution using oligonucleotide arrays. Many more of the translocations were balanced than expected, either reciprocal (eight in total) or balanced for at least one participating chromosome (19 paired breakpoints). Many breakpoints were at genes that are plausible targets of oncogenic translocation, including CTCF and P300. Two gene fusions were also demonstrated, TAX1BP1-AHCY and RIF1-PKD1L1.
Our data establish that array painting is a very effective way to map substantial numbers of translocation breakpoints and support the emerging view that chromosome rearrangements that fuse, activate or otherwise alter genes at their breakpoints may play an important role in common epithelial cancers.
Tomlins SA, et al: Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005, 310: 664-668. 10.1126/science.1117679.
Huang HE, et al: A recurrent chromosome breakpoint in breast cancer at the NRG1/neuregulin 1/heregulin gene. Cancer Res. 2004, 64: 6840-6844. 10.1158/0008-5472.CAN-04-1762.
Soda M, et al: Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007, 448: 561-566. 10.1038/nature05945.
Fiegler H, et al: Array painting: a method for the rapid analysis of aberrant chromosomes using DNA microarrays. J Med Genet. 2003, 40: 664-670. 10.1136/jmg.40.9.664.
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Cite this article
Howarth, K., Blood, K., Ng, B. et al. Chromosome translocations in breast cancer. Breast Cancer Res 10, P6 (2008). https://doi.org/10.1186/bcr1890
- Breast Cancer
- Prostate Cancer
- Breast Cancer Cell Line
- Gene Fusion
- Chromosome Translocation