McBride, D. J. et al. (2012) Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes. Journal of Pathology, 227(4), pp. 446-455. (doi: 10.1002/path.4042) (PMID:22514011) (PMCID:PMC3428857)
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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.
| Item Type: | Articles |
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| Additional Information: | <br>The authors, and Australian Ovarian Cancer Study Group.</br> <br>PAF and MRS would like to acknowledge the Wellcome Trust for support (Grant No. 077012/Z/05/Z). DDLB acknowledges the National Health and Medical Research Council (NHMRC) for funding support (Project Grant No. 628779). JDB would like to acknowledge Cancer Research UK for funding, and support from the University of Cambridge, Hutchison Whampoa Ltd, the Cambridge Experimental Cancer Medicine Centre and the NIHR Biomedical Research Centre. The Australian Ovarian Cancer Study was supported by the US Army Medical Research and Materiel Command (Grant No. DAMD17-01-1-0729), the Cancer Council Tasmania, the Cancer Foundation of Western Australia and the National Health and Medical Research Council of Australia.</br> |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Cooke, Dr Susie |
| Authors: | 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., Caubit, X., Stratton, M. R., Brenton, J. D., Campbell, P. J., Futreal, P. A., and Bowtell, D. D.L. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Journal of Pathology |
| Publisher: | Wiley |
| ISSN: | 0022-3417 |
| ISSN (Online): | 1096-9896 |
| Published Online: | 06 June 2012 |
| Copyright Holders: | Copyright © 2012 Pathological Society of Great Britain and Ireland. |
| First Published: | First published in Journal of Pathology 227(4):446-455 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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