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- Title
Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes.
- Authors
McBride, David J; Etemadmoghadam, Dariush; Cooke, Susanna L; Alsop, Kathryn; George, Joshy; Butler, Adam; Cho, Juok; Galappaththige, Danushka; Greenman, Chris; Howarth, Karen D; Lau, King W; Ng, Charlotte K; Raine, Keiran; Teague, Jon; Wedge, David C; Cancer Study Group, Australian Ovarian; Caubit, Xavier; Stratton, Michael R; Brenton, James D; Campbell, Peter J
- 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.
- Publication
Journal of Pathology, 2012, Vol 227, Issue 4, p446
- ISSN
0022-3417
- Publication type
Article
- DOI
10.1002/path.4042