Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes
Identifieur interne : 002E87 ( Istex/Corpus ); précédent : 002E86; suivant : 002E88Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes
Auteurs : 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 BowtellSource :
- The Journal of Pathology [ 0022-3417 ] ; 2012-08.
English descriptors
- KwdEn :
- Arid1a, Brca1, Brca2, Breakpoints, Cancer, Cancer genome, Cancer study, Cancer type, Carcinoma, Ccne1, Cell cancers, Clear cell, Clear cell cancers, Clin cancer, Copy number data, Copyright, Deletion, Exon, Fusion gene, Gene, Gene expression, Genome, Genomic, Germline, Germline brca1, Great britain, Hgscs, Hgscs cases, High frequency, Inversion, John wiley sons, Maccallum cancer centre, Mutation, Ovarian, Ovarian cancer, Ovarian cancers, Ovarian tumours, Pathol, Pathological society, Phenotype, Prostate cancer, Rearrangement, Sequencing, Serous, Somatic, Somatic mutations, Somatic rearrangements, Structural rearrangements, Subtypes, Tandem, Tandem duplication, Tandem duplication phenotype, Tandem duplications, Tandem duplicator phenotype, Translocation, Tshz3, Tshz3 breakpoints, Tshz3 gene expression, Tumour.
- Teeft :
- Arid1a, Brca1, Brca2, Breakpoints, Cancer, Cancer genome, Cancer study, Cancer type, Carcinoma, Ccne1, Cell cancers, Clear cell, Clear cell cancers, Clin cancer, Copy number data, Copyright, Deletion, Exon, Fusion gene, Gene, Gene expression, Genome, Genomic, Germline, Germline brca1, Great britain, Hgscs, Hgscs cases, High frequency, Inversion, John wiley sons, Maccallum cancer centre, Mutation, Ovarian, Ovarian cancer, Ovarian cancers, Ovarian tumours, Pathol, Pathological society, Phenotype, Prostate cancer, Rearrangement, Sequencing, Serous, Somatic, Somatic mutations, Somatic rearrangements, Structural rearrangements, Subtypes, Tandem, Tandem duplication, Tandem duplication phenotype, Tandem duplications, Tandem duplicator phenotype, Translocation, Tshz3, Tshz3 breakpoints, Tshz3 gene expression, Tumour.
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.
Url:
DOI: 10.1002/path.4042
Links to Exploration step
ISTEX:F8881D8FAE79660AB970D32C41E3D15E5985498FLe document en format XML
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Mcbride</name><affiliation><mods:affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence address: Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</mods:affiliation></affiliation></author><author><name sortKey="Etemadmoghadam, Dariush" sort="Etemadmoghadam, Dariush" uniqKey="Etemadmoghadam D" first="Dariush" last="Etemadmoghadam">Dariush Etemadmoghadam</name><affiliation><mods:affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pathology, University of Melbourne, Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence address: Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</mods:affiliation></affiliation></author><author><name sortKey="Cooke, Susanna L" sort="Cooke, Susanna L" uniqKey="Cooke S" first="Susanna L" last="Cooke">Susanna L. 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Mcbride</name><affiliation><mods:affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence address: Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</mods:affiliation></affiliation></author><author><name sortKey="Etemadmoghadam, Dariush" sort="Etemadmoghadam, Dariush" uniqKey="Etemadmoghadam D" first="Dariush" last="Etemadmoghadam">Dariush Etemadmoghadam</name><affiliation><mods:affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pathology, University of Melbourne, Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence address: Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</mods:affiliation></affiliation></author><author><name sortKey="Cooke, Susanna L" sort="Cooke, Susanna L" uniqKey="Cooke S" first="Susanna L" last="Cooke">Susanna L. Cooke</name><affiliation><mods:affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</mods:affiliation></affiliation><affiliation><mods:affiliation>Cancer Research UK Cambridge Research Institute, Cambridge, UK</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence address: Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</mods:affiliation></affiliation></author><author><name sortKey="Alsop, Kathryn" sort="Alsop, Kathryn" uniqKey="Alsop K" first="Kathryn" last="Alsop">Kathryn Alsop</name><affiliation><mods:affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia</mods:affiliation></affiliation></author><author><name sortKey="George, Joshy" sort="George, Joshy" uniqKey="George J" first="Joshy" last="George">Joshy George</name><affiliation><mods:affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia</mods:affiliation></affiliation></author><author><name sortKey="Butler, Adam" sort="Butler, Adam" uniqKey="Butler A" first="Adam" last="Butler">Adam Butler</name><affiliation><mods:affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</mods:affiliation></affiliation></author><author><name sortKey="Cho, Juok" sort="Cho, Juok" uniqKey="Cho J" first="Juok" last="Cho">Juok Cho</name><affiliation><mods:affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</mods:affiliation></affiliation></author><author><name sortKey="Galappaththige, Danushka" sort="Galappaththige, Danushka" uniqKey="Galappaththige D" first="Danushka" last="Galappaththige">Danushka Galappaththige</name><affiliation><mods:affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</mods:affiliation></affiliation></author><author><name sortKey="Greenman, Chris" sort="Greenman, Chris" uniqKey="Greenman C" first="Chris" last="Greenman">Chris Greenman</name><affiliation><mods:affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</mods:affiliation></affiliation></author><author><name sortKey="Howarth, Karen D" sort="Howarth, Karen D" uniqKey="Howarth K" first="Karen D" last="Howarth">Karen D. Howarth</name><affiliation><mods:affiliation>Hutchison/MRC Research Centre and Department of Pathology, University of Cambridge, UK</mods:affiliation></affiliation></author><author><name sortKey="Lau, King W" sort="Lau, King W" uniqKey="Lau K" first="King W" last="Lau">King W. Lau</name><affiliation><mods:affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</mods:affiliation></affiliation></author><author><name sortKey="Ng, Charlotte K" sort="Ng, Charlotte K" uniqKey="Ng C" first="Charlotte K" last="Ng">Charlotte K. Ng</name><affiliation><mods:affiliation>Cancer Research UK Cambridge Research Institute, Cambridge, UK</mods:affiliation></affiliation></author><author><name sortKey="Raine, Keiran" sort="Raine, Keiran" uniqKey="Raine K" first="Keiran" last="Raine">Keiran Raine</name><affiliation><mods:affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</mods:affiliation></affiliation></author><author><name sortKey="Teague, Jon" sort="Teague, Jon" uniqKey="Teague J" first="Jon" last="Teague">Jon Teague</name><affiliation><mods:affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</mods:affiliation></affiliation></author><author><name sortKey="Wedge, David C" sort="Wedge, David C" uniqKey="Wedge D" first="David C" last="Wedge">David C. Wedge</name><affiliation><mods:affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</mods:affiliation></affiliation></author><author><name sortKey="Cancer Study Group, Australian Ovarian" sort="Cancer Study Group, Australian Ovarian" uniqKey="Cancer Study Group A" first="Australian Ovarian" last="Cancer Study Group">Australian Ovarian Cancer Study Group</name><affiliation><mods:affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</mods:affiliation></affiliation></author><author><name sortKey="Caubit, Xavier" sort="Caubit, Xavier" uniqKey="Caubit X" first="Xavier" last="Caubit">Xavier Caubit</name><affiliation><mods:affiliation>Developmental Biology Institute of Marseille‐Luminy (IBDML), UMR 6216, CNRS‐Inserm‐Université de la Méditerranée, France</mods:affiliation></affiliation></author><author><name sortKey="Stratton, Michael R" sort="Stratton, Michael R" uniqKey="Stratton M" first="Michael R" last="Stratton">Michael R. Stratton</name><affiliation><mods:affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</mods:affiliation></affiliation></author><author><name sortKey="Brenton, James D" sort="Brenton, James D" uniqKey="Brenton J" first="James D" last="Brenton">James D. Brenton</name><affiliation><mods:affiliation>Cancer Research UK Cambridge Research Institute, Cambridge, UK</mods:affiliation></affiliation></author><author><name sortKey="Campbell, Peter J" sort="Campbell, Peter J" uniqKey="Campbell P" first="Peter J" last="Campbell">Peter J. Campbell</name><affiliation><mods:affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</mods:affiliation></affiliation></author><author><name sortKey="Futreal, P Andrew" sort="Futreal, P Andrew" uniqKey="Futreal P" first="P Andrew" last="Futreal">P Andrew Futreal</name><affiliation><mods:affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</mods:affiliation></affiliation></author><author><name sortKey="Bowtell, David Dl" sort="Bowtell, David Dl" uniqKey="Bowtell D" first="David Dl" last="Bowtell">David Dl Bowtell</name><affiliation><mods:affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: david.bowtell@petermac.org</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence address: Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">The Journal of Pathology</title><title level="j" type="alt">JOURNAL OF PATHOLOGY, THE</title><idno type="ISSN">0022-3417</idno><idno type="eISSN">1096-9896</idno><imprint><biblScope unit="vol">227</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="446">446</biblScope><biblScope unit="page" to="455">455</biblScope><biblScope unit="page-count">10</biblScope><publisher>John Wiley & Sons, Ltd.</publisher><pubPlace>Chichester, UK</pubPlace><date type="published" when="2012-08">2012-08</date></imprint><idno type="ISSN">0022-3417</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-3417</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Arid1a</term><term>Brca1</term><term>Brca2</term><term>Breakpoints</term><term>Cancer</term><term>Cancer genome</term><term>Cancer study</term><term>Cancer type</term><term>Carcinoma</term><term>Ccne1</term><term>Cell cancers</term><term>Clear cell</term><term>Clear cell cancers</term><term>Clin cancer</term><term>Copy number data</term><term>Copyright</term><term>Deletion</term><term>Exon</term><term>Fusion gene</term><term>Gene</term><term>Gene expression</term><term>Genome</term><term>Genomic</term><term>Germline</term><term>Germline brca1</term><term>Great britain</term><term>Hgscs</term><term>Hgscs cases</term><term>High frequency</term><term>Inversion</term><term>John wiley sons</term><term>Maccallum cancer centre</term><term>Mutation</term><term>Ovarian</term><term>Ovarian cancer</term><term>Ovarian cancers</term><term>Ovarian tumours</term><term>Pathol</term><term>Pathological society</term><term>Phenotype</term><term>Prostate cancer</term><term>Rearrangement</term><term>Sequencing</term><term>Serous</term><term>Somatic</term><term>Somatic mutations</term><term>Somatic rearrangements</term><term>Structural rearrangements</term><term>Subtypes</term><term>Tandem</term><term>Tandem duplication</term><term>Tandem duplication phenotype</term><term>Tandem duplications</term><term>Tandem duplicator phenotype</term><term>Translocation</term><term>Tshz3</term><term>Tshz3 breakpoints</term><term>Tshz3 gene expression</term><term>Tumour</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Arid1a</term><term>Brca1</term><term>Brca2</term><term>Breakpoints</term><term>Cancer</term><term>Cancer genome</term><term>Cancer study</term><term>Cancer type</term><term>Carcinoma</term><term>Ccne1</term><term>Cell cancers</term><term>Clear cell</term><term>Clear cell cancers</term><term>Clin cancer</term><term>Copy number data</term><term>Copyright</term><term>Deletion</term><term>Exon</term><term>Fusion gene</term><term>Gene</term><term>Gene expression</term><term>Genome</term><term>Genomic</term><term>Germline</term><term>Germline brca1</term><term>Great britain</term><term>Hgscs</term><term>Hgscs cases</term><term>High frequency</term><term>Inversion</term><term>John wiley sons</term><term>Maccallum cancer centre</term><term>Mutation</term><term>Ovarian</term><term>Ovarian cancer</term><term>Ovarian cancers</term><term>Ovarian tumours</term><term>Pathol</term><term>Pathological society</term><term>Phenotype</term><term>Prostate cancer</term><term>Rearrangement</term><term>Sequencing</term><term>Serous</term><term>Somatic</term><term>Somatic mutations</term><term>Somatic rearrangements</term><term>Structural rearrangements</term><term>Subtypes</term><term>Tandem</term><term>Tandem duplication</term><term>Tandem duplication phenotype</term><term>Tandem duplications</term><term>Tandem duplicator phenotype</term><term>Translocation</term><term>Tshz3</term><term>Tshz3 breakpoints</term><term>Tshz3 gene expression</term><term>Tumour</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>rearrangement</json:string><json:string>ovarian</json:string><json:string>tshz3</json:string><json:string>mutation</json:string><json:string>hgscs</json:string><json:string>serous</json:string><json:string>tumour</json:string><json:string>genome</json:string><json:string>exon</json:string><json:string>breakpoints</json:string><json:string>brca1</json:string><json:string>tandem</json:string><json:string>genomic</json:string><json:string>deletion</json:string><json:string>ccne1</json:string><json:string>germline</json:string><json:string>sequencing</json:string><json:string>pathol</json:string><json:string>phenotype</json:string><json:string>brca2</json:string><json:string>ovarian cancer</json:string><json:string>copyright</json:string><json:string>pathological society</json:string><json:string>great britain</json:string><json:string>john wiley 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cancers</json:string><json:string>somatic rearrangements</json:string><json:string>cancer type</json:string><json:string>somatic mutations</json:string><json:string>tshz3 gene expression</json:string><json:string>tshz3 breakpoints</json:string><json:string>high frequency</json:string><json:string>fusion gene</json:string><json:string>tandem duplicator phenotype</json:string><json:string>inversion</json:string><json:string>cancer</json:string></teeft></keywords><author><json:item><name>David J McBride</name><affiliations><json:string>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</json:string><json:string>Correspondence address: Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</json:string></affiliations></json:item><json:item><name>Dariush Etemadmoghadam</name><affiliations><json:string>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</json:string><json:string>Department of Pathology, University of Melbourne, Australia</json:string><json:string>Correspondence address: Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</json:string></affiliations></json:item><json:item><name>Susanna L Cooke</name><affiliations><json:string>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</json:string><json:string>Cancer Research UK Cambridge Research Institute, Cambridge, UK</json:string><json:string>Correspondence address: Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</json:string></affiliations></json:item><json:item><name>Kathryn Alsop</name><affiliations><json:string>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</json:string><json:string>Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia</json:string></affiliations></json:item><json:item><name>Joshy George</name><affiliations><json:string>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</json:string><json:string>Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia</json:string></affiliations></json:item><json:item><name>Adam Butler</name><affiliations><json:string>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</json:string></affiliations></json:item><json:item><name>Juok Cho</name><affiliations><json:string>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</json:string></affiliations></json:item><json:item><name>Danushka Galappaththige</name><affiliations><json:string>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</json:string></affiliations></json:item><json:item><name>Chris Greenman</name><affiliations><json:string>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</json:string></affiliations></json:item><json:item><name>Karen D Howarth</name><affiliations><json:string>Hutchison/MRC Research Centre and Department of Pathology, University of Cambridge, UK</json:string></affiliations></json:item><json:item><name>King W Lau</name><affiliations><json:string>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</json:string></affiliations></json:item><json:item><name>Charlotte K Ng</name><affiliations><json:string>Cancer Research UK Cambridge Research Institute, Cambridge, UK</json:string></affiliations></json:item><json:item><name>Keiran Raine</name><affiliations><json:string>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</json:string></affiliations></json:item><json:item><name>Jon Teague</name><affiliations><json:string>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</json:string></affiliations></json:item><json:item><name>David C Wedge</name><affiliations><json:string>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</json:string></affiliations></json:item><json:item><name>Australian Ovarian Cancer Study Group</name><affiliations><json:string>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</json:string></affiliations></json:item><json:item><name>Xavier Caubit</name><affiliations><json:string>Developmental Biology Institute of Marseille‐Luminy (IBDML), UMR 6216, CNRS‐Inserm‐Université de la Méditerranée, France</json:string></affiliations></json:item><json:item><name>Michael R Stratton</name><affiliations><json:string>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</json:string></affiliations></json:item><json:item><name>James D Brenton</name><affiliations><json:string>Cancer Research UK Cambridge Research Institute, Cambridge, UK</json:string></affiliations></json:item><json:item><name>Peter J Campbell</name><affiliations><json:string>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</json:string></affiliations></json:item><json:item><name>P Andrew Futreal</name><affiliations><json:string>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</json:string></affiliations></json:item><json:item><name>David DL Bowtell</name><affiliations><json:string>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</json:string><json:string>Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia</json:string><json:string>Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia</json:string><json:string>E-mail: david.bowtell@petermac.org</json:string><json:string>Correspondence address: Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>ovarian cancer</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>structural rearrangements</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>TSHZ3</value></json:item></subject><articleId><json:string>PATH4042</json:string></articleId><arkIstex>ark:/67375/WNG-F5H6WDCG-8</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><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.</abstract><qualityIndicators><score>9.532</score><pdfWordCount>5697</pdfWordCount><pdfCharCount>39283</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>10</pdfPageCount><pdfPageSize>595 x 842 pts (A4)</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>211</abstractWordCount><abstractCharCount>1544</abstractCharCount><keywordCount>3</keywordCount></qualityIndicators><title>Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes</title><pmid><json:string>22514011</json:string></pmid><genre><json:string>article</json:string></genre><host><title>The Journal of 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City</json:string><json:string>Australia</json:string><json:string>Melbourne</json:string><json:string>USA</json:string><json:string>Wales</json:string><json:string>CA</json:string><json:string>Ireland</json:string><json:string>Marseille</json:string><json:string>Cambridge</json:string><json:string>Hobart</json:string></placeName><ref_url><json:string>http://www.ebi.ac.uk/ega/</json:string></ref_url><ref_bibl><json:string>[4]</json:string><json:string>[10,11]</json:string><json:string>[23]</json:string><json:string>[15,16]</json:string><json:string>[29]</json:string><json:string>[22]</json:string><json:string>[8]</json:string><json:string>Wiegand et al</json:string><json:string>[39]</json:string><json:string>[1]</json:string><json:string>[32]</json:string><json:string>McBride et al</json:string><json:string>[30,31]</json:string><json:string>Salzman et al</json:string><json:string>[8,9]</json:string><json:string>[38]</json:string><json:string>[3]</json:string><json:string>Alsop et 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Forensic Medicine</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string></inist></categories><publicationDate>2012</publicationDate><copyrightDate>2012</copyrightDate><doi><json:string>10.1002/path.4042</json:string></doi><id>F8881D8FAE79660AB970D32C41E3D15E5985498F</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/F8881D8FAE79660AB970D32C41E3D15E5985498F/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/F8881D8FAE79660AB970D32C41E3D15E5985498F/fulltext/zip</uri></json:item><istex:fulltextTEI 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Published by John Wiley & Sons, Ltd.</licence></availability><date type="published" when="2012-08"></date></publicationStmt><notesStmt><note type="content-type" subtype="article" source="article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</note><note type="publication-type" subtype="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note></notesStmt><sourceDesc><biblStruct type="article"><analytic><title level="a" type="main" xml:lang="en">Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes<ref type="note" target="#fn4"></ref></title><title level="a" type="short" xml:lang="en">Structural rearrangements in ovarian tumours</title><author xml:id="author-0000" role="corresp"><persName><forename type="first">David J</forename><surname>McBride</surname></persName><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK<address><country key="GB"></country></address></affiliation><note type="foot">Joint first authors.</note><affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</affiliation></author><author xml:id="author-0001" role="corresp"><persName><forename type="first">Dariush</forename><surname>Etemadmoghadam</surname></persName><affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia<address><country key="AU"></country></address></affiliation><affiliation>Department of Pathology, University of Melbourne, Australia<address><country key="AU"></country></address></affiliation><note type="foot">Joint first authors.</note><affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</affiliation></author><author xml:id="author-0002" role="corresp"><persName><forename type="first">Susanna L</forename><surname>Cooke</surname></persName><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK<address><country key="GB"></country></address></affiliation><affiliation>Cancer Research UK Cambridge Research Institute, Cambridge, UK<address><country key="GB"></country></address></affiliation><note type="foot">Joint first authors.</note><affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Kathryn</forename><surname>Alsop</surname></persName><affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia<address><country key="AU"></country></address></affiliation><affiliation>Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia<address><country key="AU"></country></address></affiliation></author><author xml:id="author-0004"><persName><forename type="first">Joshy</forename><surname>George</surname></persName><affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia<address><country key="AU"></country></address></affiliation><affiliation>Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia<address><country key="AU"></country></address></affiliation></author><author xml:id="author-0005"><persName><forename type="first">Adam</forename><surname>Butler</surname></persName><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK<address><country key="GB"></country></address></affiliation></author><author xml:id="author-0006"><persName><forename type="first">Juok</forename><surname>Cho</surname></persName><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK<address><country key="GB"></country></address></affiliation></author><author xml:id="author-0007"><persName><forename type="first">Danushka</forename><surname>Galappaththige</surname></persName><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK<address><country key="GB"></country></address></affiliation></author><author xml:id="author-0008"><persName><forename type="first">Chris</forename><surname>Greenman</surname></persName><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK<address><country key="GB"></country></address></affiliation></author><author xml:id="author-0009"><persName><forename type="first">Karen D</forename><surname>Howarth</surname></persName><affiliation>Hutchison/MRC Research Centre and Department of Pathology, University of Cambridge, UK<address><country key="GB"></country></address></affiliation></author><author xml:id="author-0010"><persName><forename type="first">King W</forename><surname>Lau</surname></persName><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK<address><country key="GB"></country></address></affiliation></author><author xml:id="author-0011"><persName><forename type="first">Charlotte K</forename><surname>Ng</surname></persName><affiliation>Cancer Research UK Cambridge Research Institute, Cambridge, UK<address><country key="GB"></country></address></affiliation></author><author xml:id="author-0012"><persName><forename type="first">Keiran</forename><surname>Raine</surname></persName><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK<address><country key="GB"></country></address></affiliation></author><author xml:id="author-0013"><persName><forename type="first">Jon</forename><surname>Teague</surname></persName><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK<address><country key="GB"></country></address></affiliation></author><author xml:id="author-0014"><persName><forename type="first">David C</forename><surname>Wedge</surname></persName><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK<address><country key="GB"></country></address></affiliation></author><author xml:id="author-0015"><persName><forename type="first">Australian Ovarian</forename><surname>Cancer Study Group</surname></persName><affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia<address><country key="AU"></country></address></affiliation></author><author xml:id="author-0016"><persName><forename type="first">Xavier</forename><surname>Caubit</surname></persName><affiliation>Developmental Biology Institute of Marseille‐Luminy (IBDML), UMR 6216, CNRS‐Inserm‐Université de la Méditerranée, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0017"><persName><forename type="first">Michael R</forename><surname>Stratton</surname></persName><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK<address><country key="GB"></country></address></affiliation></author><author xml:id="author-0018"><persName><forename type="first">James D</forename><surname>Brenton</surname></persName><affiliation>Cancer Research UK Cambridge Research Institute, Cambridge, UK<address><country key="GB"></country></address></affiliation></author><author xml:id="author-0019"><persName><forename type="first">Peter J</forename><surname>Campbell</surname></persName><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK<address><country key="GB"></country></address></affiliation></author><author xml:id="author-0020"><persName><forename type="first">P Andrew</forename><surname>Futreal</surname></persName><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK<address><country key="GB"></country></address></affiliation><note type="foot">Joint senior authors.</note></author><author xml:id="author-0021" role="corresp"><persName><forename type="first">David DL</forename><surname>Bowtell</surname></persName><email>david.bowtell@petermac.org</email><affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia<address><country key="AU"></country></address></affiliation><affiliation>Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia<address><country key="AU"></country></address></affiliation><affiliation>Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia<address><country key="AU"></country></address></affiliation><note type="foot">Joint senior authors.</note><affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</affiliation></author><idno type="istex">F8881D8FAE79660AB970D32C41E3D15E5985498F</idno><idno type="ark">ark:/67375/WNG-F5H6WDCG-8</idno><idno type="DOI">10.1002/path.4042</idno><idno type="unit">PATH4042</idno><idno type="toTypesetVersion">file:PATH.PATH4042.pdf</idno></analytic><monogr><title level="j" type="main">The Journal of Pathology</title><title level="j" type="alt">JOURNAL OF PATHOLOGY, THE</title><idno type="pISSN">0022-3417</idno><idno type="eISSN">1096-9896</idno><idno type="book-DOI">10.1002/(ISSN)1096-9896</idno><idno type="book-part-DOI">10.1002/path.v227.4</idno><idno type="product">PATH</idno><imprint><biblScope unit="vol">227</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="446">446</biblScope><biblScope unit="page" to="455">455</biblScope><biblScope unit="page-count">10</biblScope><publisher>John Wiley & Sons, Ltd.</publisher><pubPlace>Chichester, UK</pubPlace><date type="published" when="2012-08"></date></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><abstract xml:lang="en" style="main"><head>Abstract</head><p>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, <hi rend="italic">TSHZ3,</hi> 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 <hi rend="italic">BRCA1/2</hi> mutation, suggesting that other common mechanisms or carcinogenic exposures are operative. High‐grade serous cancers arising in women with germline <hi rend="italic">BRCA1</hi> or <hi rend="italic">BRCA2</hi> mutation showed a high frequency of small chromosomal deletions. These findings indicate that <hi rend="italic">BRCA1/2</hi> 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. 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Published by John Wiley & Sons, Ltd.</copyright><eventGroup><event type="manuscriptReceived" date="2012-01-25"></event><event type="manuscriptRevised" date="2012-04-06"></event><event type="manuscriptAccepted" date="2012-04-07"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:3.1.6 mode:FullText" date="2012-08-01"></event><event type="publishedOnlineAccepted" date="2012-06-12"></event><event type="publishedOnlineEarlyUnpaginated" date="2012-07-02"></event><event type="publishedOnlineFinalForm" date="2012-07-10"></event><event type="firstOnline" date="2012-07-02"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-06"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.3.4 mode:FullText" date="2015-02-24"></event></eventGroup><numberingGroup><numbering type="pageFirst">446</numbering><numbering type="pageLast">455</numbering></numberingGroup><correspondenceTo>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:PATH.PATH4042.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="2"></count><count type="tableTotal" number="2"></count><count type="referenceTotal" number="45"></count></countGroup><titleGroup><title type="main" xml:lang="en">Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes<link href="#fn4"></link></title><title type="short" xml:lang="en">Structural rearrangements in ovarian tumours</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" corresponding="yes" noteRef="#fn2"><personName><givenNames>David J</givenNames><familyName>McBride</familyName></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2 #af3" corresponding="yes" noteRef="#fn2"><personName><givenNames>Dariush</givenNames><familyName>Etemadmoghadam</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1 #af4" corresponding="yes" noteRef="#fn2"><personName><givenNames>Susanna L</givenNames><familyName>Cooke</familyName></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af2 #af5"><personName><givenNames>Kathryn</givenNames><familyName>Alsop</familyName></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af2 #af5"><personName><givenNames>Joshy</givenNames><familyName>George</familyName></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Adam</givenNames><familyName>Butler</familyName></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Juok</givenNames><familyName>Cho</familyName></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Danushka</givenNames><familyName>Galappaththige</familyName></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Chris</givenNames><familyName>Greenman</familyName></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af6"><personName><givenNames>Karen D</givenNames><familyName>Howarth</familyName></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af1"><personName><givenNames>King W</givenNames><familyName>Lau</familyName></personName></creator><creator xml:id="au12" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Charlotte K</givenNames><familyName>Ng</familyName></personName></creator><creator xml:id="au13" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Keiran</givenNames><familyName>Raine</familyName></personName></creator><creator xml:id="au14" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Jon</givenNames><familyName>Teague</familyName></personName></creator><creator xml:id="au15" creatorRole="author" affiliationRef="#af1"><personName><givenNames>David C</givenNames><familyName>Wedge</familyName></personName></creator><creator xml:id="au16" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Australian Ovarian</givenNames><familyName>Cancer Study Group</familyName></personName></creator><creator xml:id="au17" creatorRole="author" affiliationRef="#af7"><personName><givenNames>Xavier</givenNames><familyName>Caubit</familyName></personName></creator><creator xml:id="au18" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Michael R</givenNames><familyName>Stratton</familyName></personName></creator><creator xml:id="au19" creatorRole="author" affiliationRef="#af4"><personName><givenNames>James D</givenNames><familyName>Brenton</familyName></personName></creator><creator xml:id="au20" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Peter J</givenNames><familyName>Campbell</familyName></personName></creator><creator xml:id="au21" creatorRole="author" affiliationRef="#af1" noteRef="#fn3"><personName><givenNames>P Andrew</givenNames><familyName>Futreal</familyName></personName></creator><creator xml:id="au22" creatorRole="author" affiliationRef="#af2 #af5 #af8" corresponding="yes" noteRef="#fn3"><personName><givenNames>David DL</givenNames><familyName>Bowtell</familyName></personName><contactDetails><email>david.bowtell@petermac.org</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="GB" type="organization"><unparsedAffiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="AU" type="organization"><unparsedAffiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="AU" type="organization"><unparsedAffiliation>Department of Pathology, University of Melbourne, Australia</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="GB" type="organization"><unparsedAffiliation>Cancer Research UK Cambridge Research Institute, Cambridge, UK</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="AU" type="organization"><unparsedAffiliation>Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="GB" type="organization"><unparsedAffiliation>Hutchison/MRC Research Centre and Department of Pathology, University of Cambridge, UK</unparsedAffiliation></affiliation><affiliation xml:id="af7" countryCode="FR" type="organization"><unparsedAffiliation>Developmental Biology Institute of Marseille‐Luminy (IBDML), UMR 6216, CNRS‐Inserm‐Université de la Méditerranée, France</unparsedAffiliation></affiliation><affiliation xml:id="af8" countryCode="AU" type="organization"><unparsedAffiliation>Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">ovarian cancer</keyword><keyword xml:id="kwd2">structural rearrangements</keyword><keyword xml:id="kwd3"><i>TSHZ3</i></keyword></keywordGroup><supportingInformation><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:00223417:media:path4042:path_4042_sm_suppinfofigs1"></mediaResource><caption>Supporting Information: Figure S1. Analysis of TSHZ3 gene expression in AOCS and TCGA datasets.</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:00223417:media:path4042:path_4042_sm_suppinfotabs1"></mediaResource><caption>Supporting Information: Table S1. Sample details.</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:00223417:media:path4042:path_4042_sm_suppinfotabs2"></mediaResource><caption>Supporting Information: Table S2. Summary of somatic rearrangements found in 13 ovarian cancers.</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:00223417:media:path4042:path_4042_sm_suppinfotabs3"></mediaResource><caption>Supporting Information: Table S3. Breakpoints in known genes.</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:00223417:media:path4042:path_4042_sm_suppinfotabs4"></mediaResource><caption>Supporting Information: Table S4. Primer sequences.</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:00223417:media:path4042:path_4042_sm_suppinfotabs5"></mediaResource><caption>Supporting Information: Table S5. Tumour cell content predicted by ASCAT and PICNIC.</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:00223417:media:path4042:path_4042_sm_suppinfosm"></mediaResource><caption>Supporting Information: Supplementary methods</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:00223417:media:path4042:path_4042_sm_suppinfo"></mediaResource><caption>Supporting Information: Legend to Figure S1</caption></supportingInfoItem></supportingInformation><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>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, <i>TSHZ3,</i> 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 <i>BRCA1/2</i> mutation, suggesting that other common mechanisms or carcinogenic exposures are operative. High‐grade serous cancers arising in women with germline <i>BRCA1</i> or <i>BRCA2</i> mutation showed a high frequency of small chromosomal deletions. These findings indicate that <i>BRCA1/2</i> 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.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn4"><p>No conflicts of interest were declared.</p></note><note xml:id="fn2"><p>Joint first authors.</p></note><note xml:id="fn3"><p>Joint senior authors.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Structural rearrangements in ovarian tumours</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes</title></titleInfo><name type="personal"><namePart type="given">David J</namePart><namePart type="family">McBride</namePart><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</affiliation><description>Joint first authors.</description><affiliation>Correspondence address: Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dariush</namePart><namePart type="family">Etemadmoghadam</namePart><affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</affiliation><affiliation>Department of Pathology, University of Melbourne, Australia</affiliation><description>Joint first authors.</description><affiliation>Correspondence address: Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Susanna L</namePart><namePart type="family">Cooke</namePart><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</affiliation><affiliation>Cancer Research UK Cambridge Research Institute, Cambridge, UK</affiliation><description>Joint first authors.</description><affiliation>Correspondence address: Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kathryn</namePart><namePart type="family">Alsop</namePart><affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</affiliation><affiliation>Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Joshy</namePart><namePart type="family">George</namePart><affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</affiliation><affiliation>Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Adam</namePart><namePart type="family">Butler</namePart><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Juok</namePart><namePart type="family">Cho</namePart><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Danushka</namePart><namePart type="family">Galappaththige</namePart><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Chris</namePart><namePart type="family">Greenman</namePart><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Karen D</namePart><namePart type="family">Howarth</namePart><affiliation>Hutchison/MRC Research Centre and Department of Pathology, University of Cambridge, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">King W</namePart><namePart type="family">Lau</namePart><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Charlotte K</namePart><namePart type="family">Ng</namePart><affiliation>Cancer Research UK Cambridge Research Institute, Cambridge, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Keiran</namePart><namePart type="family">Raine</namePart><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jon</namePart><namePart type="family">Teague</namePart><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David C</namePart><namePart type="family">Wedge</namePart><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Australian Ovarian</namePart><namePart type="family">Cancer Study Group</namePart><affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Xavier</namePart><namePart type="family">Caubit</namePart><affiliation>Developmental Biology Institute of Marseille‐Luminy (IBDML), UMR 6216, CNRS‐Inserm‐Université de la Méditerranée, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael R</namePart><namePart type="family">Stratton</namePart><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">James D</namePart><namePart type="family">Brenton</namePart><affiliation>Cancer Research UK Cambridge Research Institute, Cambridge, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter J</namePart><namePart type="family">Campbell</namePart><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P Andrew</namePart><namePart type="family">Futreal</namePart><affiliation>Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK</affiliation><description>Joint senior authors.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David DL</namePart><namePart type="family">Bowtell</namePart><affiliation>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia</affiliation><affiliation>Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia</affiliation><affiliation>Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia</affiliation><description>Joint senior authors.</description><affiliation>E-mail: david.bowtell@petermac.org</affiliation><affiliation>Correspondence address: Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Australia.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>John Wiley & Sons, Ltd.</publisher><place><placeTerm type="text">Chichester, UK</placeTerm></place><dateIssued encoding="w3cdtf">2012-08</dateIssued><dateCaptured encoding="w3cdtf">2012-01-25</dateCaptured><dateValid encoding="w3cdtf">2012-04-07</dateValid><copyrightDate encoding="w3cdtf">2012</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="figures">2</extent><extent unit="tables">2</extent><extent unit="references">45</extent></physicalDescription><abstract lang="en">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.</abstract><note type="additional physical form">Supporting Information: Figure S1. Analysis of TSHZ3 gene expression in AOCS and TCGA datasets.Supporting Information: Table S1. Sample details.Supporting Information: Table S2. Summary of somatic rearrangements found in 13 ovarian cancers.Supporting Information: Table S3. Breakpoints in known genes.Supporting Information: Table S4. Primer sequences.Supporting Information: Table S5. Tumour cell content predicted by ASCAT and PICNIC.Supporting Information: Supplementary methodsSupporting Information: Legend to Figure S1</note><note type="content">*No conflicts of interest were declared.</note><subject lang="en"><genre>keywords</genre><topic>ovarian cancer</topic><topic>structural rearrangements</topic><topic>TSHZ3</topic></subject><relatedItem type="host"><titleInfo><title>The Journal of Pathology</title></titleInfo><titleInfo type="abbreviated"><title>J. 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