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  • Oncogenomics
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Array painting reveals a high frequency of balanced translocations in breast cancer cell lines that break in cancer-relevant genes

Oncogene volume 27, pages 3345–3359 (2008)Cite this article

Abstract

Chromosome translocations in the common epithelial cancers are abundant, yet little is known about them. They have been thought to be almost all unbalanced and therefore dismissed as mostly mediating tumour suppressor loss. 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 bacterial artificial chromosome (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 at 1 Mb resolution than expected, either reciprocal (eight in total) or balanced for at least one participating chromosome (19 paired breakpoints). Second, many of the breakpoints were at genes that are plausible targets of oncogenic translocation, including balanced breaks at CTCF, EP300/p300 and FOXP4. Two gene fusions were demonstrated, TAX1BP1–AHCY and RIF1–PKD1L1. Our results support the idea that chromosome rearrangements may play an important role in common epithelial cancers such as breast cancer.

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Acknowledgements

We thank Mira Grigorova for unpublished SKY data; Elizabeth Batty for help with array analysis; Danita Pearson, Martin McCabe, Wellcome Trust Sanger Institute Microarray Facility, CRUK Microarray Facility, Institute of Cancer Research and University of Cambridge Department of Pathology Microarray Facility for array production. This work was supported by Cancer Research UK; Breast Cancer Campaign, Breast Cancer Research Trust; Samantha Dickson Brain Tumour Trust; Wellcome Trust (NPC, BLN) and studentships from Cambridge Commonwealth Trust and the Sackler Foundation (KAB) and MRC (SLC).

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Authors and Affiliations

  1. Department of Pathology, Hutchison-MRC Research Centre, University of Cambridge, Cambridge, UK

    K D Howarth, K A Blood, J C Beavis, Y Chua, S L Cooke, S Raby & P A W Edwards

  2. Wellcome Trust Sanger Institute, Cambridge, UK

    B L Ng & N P Carter

  3. Department of Pathology, Division of Molecular Histopathology, Addenbrookes Hospital, University of Cambridge, Cambridge, UK

    K Ichimura & V P Collins

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  1. K D Howarth
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  2. K A Blood
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Correspondence to P A W Edwards.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Howarth, K., Blood, K., Ng, B. et al. Array painting reveals a high frequency of balanced translocations in breast cancer cell lines that break in cancer-relevant genes. Oncogene 27, 3345–3359 (2008). https://doi.org/10.1038/sj.onc.1210993

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