Volume 8 Supplement 2

Breast cancer research: the past and the future

Open Access

Chromosome translocations may play a significant role in breast cancer

  • KL Howarth1,
  • KA Blood1,
  • JC Pole1,
  • SL Cooke1,
  • Y-L Chua1,
  • JC Beavis1,
  • B-L Ng2 and
  • PAW Edwards1
Breast Cancer Research20068(Suppl 2):S6

https://doi.org/10.1186/bcr1549

Published: 01 November 2006

Chromosome translocations that form fusion transcripts and/or activate expression of genes by promoter insertion are key events in leukaemias and lymphomas, and mesenchymal tumours, but it has been fashionable to think they are irrelevant to the common epithelial cancers such as breast cancer. However, that view is now being challenged [14]; in particular, we have shown that NRG1 is translocated in breast cancers [3]. It seems likely that some translocations in breast cancers target specific genes at their breakpoints, and this is particularly likely for reciprocal translocations.

We are cataloguing translocation breakpoints in breast cancer cell lines and tumours. We use array painting, in which individual chromosomes are purified in a cell sorter and their DNA hybridized to microarrays. We have analysed all the chromosomes of three breast cancer lines to 1 Mb resolution or better.

A striking finding was that reciprocal and more complex balanced translocations are far more frequent than expected. Together the three lines had at least 14 balanced translocations, almost three times more than identified by cytogenetics — the cryptic ones involved small fragments, or were obscured by subsequent rearrangement. Furthermore, several translocation breaks were in genes, including known cancer-critical genes such as EP300/p300 and CTCF. This supports the emerging idea that chromosome rearrangement plays a major role in the gene changes that cause breast cancer.

Authors’ Affiliations

(1)
Hutchison-MRC Research Centre, University of Cambridge
(2)
Sanger Institute

References

  1. Mitelman F, Johansson B, Mertens F: Fusion genes and rearranged genes as a linear function of chromosome aberrations in cancer. Nat Genet. 2004, 36: 331-334. 10.1038/ng1335.View ArticlePubMedGoogle Scholar
  2. Hahn Y, Bera TK, Gehlhaus K, Kirsch IR, Pastan IH, Lee B: Finding fusion genes resulting from chromosome rearrangement by analyzing the expressed sequence databases. Proc Natl Acad Sci USA. 2004, 101: 13257-13261. 10.1073/pnas.0405490101.View ArticlePubMedPubMed CentralGoogle Scholar
  3. Huang HE, Chin SF, Ginestier C, Bardou VJ, Adelaide J, Iyer NG, Garcia MJ, Pole JC, Callagy GM, Hewitt SM, 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.View ArticlePubMedGoogle Scholar
  4. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, et al: Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005, 310: 644-648. 10.1126/science.1117679.View ArticlePubMedGoogle Scholar

Copyright

© BioMed Central Ltd 2006

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