Original Paper

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Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes†

  1. David J McBride1,‡,*,
  2. Dariush Etemadmoghadam2,3,‡,*,
  3. Susanna L Cooke1,4,‡,*,
  4. Kathryn Alsop2,5,
  5. Joshy George2,5,
  6. Adam Butler1,
  7. Juok Cho1,
  8. Danushka Galappaththige1,
  9. Chris Greenman1,
  10. Karen D Howarth6,
  11. King W Lau1,
  12. Charlotte K Ng4,
  13. Keiran Raine1,
  14. Jon Teague1,
  15. David C Wedge1,
  16. Australian Ovarian Cancer Study Group2,
  17. Xavier Caubit7,
  18. Michael R Stratton1,
  19. James D Brenton4,
  20. Peter J Campbell1,
  21. P Andrew Futreal1,§,
  22. David DL Bowtell2,5,8,§,*

Article first published online: 6 JUN 2012

DOI: 10.1002/path.4042

Issue

The Journal of Pathology

The Journal of Pathology

Volume 227, Issue 4, pages 446–455, August 2012

Additional Information

How to Cite

McBride, D. J., Etemadmoghadam, D., Cooke, S. L., Alsop, K., George, J., Butler, A., Cho, J., Galappaththige, D., Greenman, C., Howarth, K. D., Lau, K. W., Ng, C. K., Raine, K., Teague, J., Wedge, D. C., Cancer Study Group, A. O., Caubit, X., Stratton, M. R., Brenton, J. D., Campbell, P. J., Futreal, P. A. and Bowtell, D. D. (2012), Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes. J. Pathol., 227: 446–455. doi: 10.1002/path.4042

Author Information

  1. 1

    Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK

  2. 2

    Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia

  3. 3

    Department of Pathology, University of Melbourne, Australia

  4. 4

    Cancer Research UK Cambridge Research Institute, Cambridge, UK

  5. 5

    Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia

  6. 6

    Hutchison/MRC Research Centre and Department of Pathology, University of Cambridge, UK

  7. 7

    Developmental Biology Institute of Marseille-Luminy (IBDML), UMR 6216, CNRS-Inserm-Université de la Méditerranée, France

  8. 8

    Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia

  1. ‡

    Joint first authors.

  2. §

    Joint senior authors.

*Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.

  1. †

    No conflicts of interest were declared.

  2. ‡

    Joint first authors.

  3. §

    Joint senior authors.

Publication History

  1. Issue published online: 10 JUL 2012
  2. Article first published online: 6 JUN 2012
  3. Accepted manuscript online: 18 APR 2012 06:45AM EST
  4. Manuscript Accepted: 7 APR 2012
  5. Manuscript Revised: 6 APR 2012
  6. Manuscript Received: 25 JAN 2012

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Keywords:

  • ovarian cancer;
  • structural rearrangements;
  • TSHZ3

Abstract

The application of paired-end next generation sequencing approaches has made it possible to systematically characterize rearrangements of the cancer genome to base-pair level. Utilizing this approach, we report the first detailed analysis of ovarian cancer rearrangements, comparing high-grade serous and clear cell cancers, and these histotypes with other solid cancers. Somatic rearrangements were systematically characterized in eight high-grade serous and five clear cell ovarian cancer genomes and we report here the identification of > 600 somatic rearrangements. Recurrent rearrangements of the transcriptional regulator gene, TSHZ3, were found in three of eight serous cases. Comparison to breast, pancreatic and prostate cancer genomes revealed that a subset of ovarian cancers share a marked tandem duplication phenotype with triple-negative breast cancers. The tandem duplication phenotype was not linked to BRCA1/2 mutation, suggesting that other common mechanisms or carcinogenic exposures are operative. High-grade serous cancers arising in women with germline BRCA1 or BRCA2 mutation showed a high frequency of small chromosomal deletions. These findings indicate that BRCA1/2 germline mutation may contribute to widespread structural change and that other undefined mechanism(s), which are potentially shared with triple-negative breast cancer, promote tandem chromosomal duplications that sculpt the ovarian cancer genome. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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