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

David J McBride,Dariush Etemadmoghadam,Susanna L Cooke,Kathryn Alsop,Joshy George,Adam Butler,Juok Cho,Danushka Galappaththige,Chris Greenman,Karen D Howarth,King W Lau,Charlotte K Ng,Keiran Raine,Jon Teague,David C Wedge,Australian Ovarian Cancer Study Group,Xavier Caubit,Michael R Stratton,James D Brenton,Peter J Campbell,P Andrew Futreal,David Dl Bowtell

  • Journal of Pathology
  • Published in: Volume:227 Issue 4: 2012 August 01
  • 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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