Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes
Identifieur interne : 005B45 ( Main/Merge ); précédent : 005B44; suivant : 005B46Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes
Auteurs : David J. Mcbride [Royaume-Uni] ; Dariush Etemadmoghadam [Australie] ; Susanna L. Cooke [Royaume-Uni] ; Kathryn Alsop [Australie] ; Joshy George [Australie] ; Adam Butler [Royaume-Uni] ; Juok Cho [Royaume-Uni] ; Danushka Galappaththige [Royaume-Uni] ; Chris Greenman [Royaume-Uni] ; Karen D. Howarth [Royaume-Uni] ; King W. Lau [Royaume-Uni] ; Charlotte K. Ng [Royaume-Uni] ; Keiran Raine [Royaume-Uni] ; Jon Teague [Royaume-Uni] ; David C. Wedge [Royaume-Uni] ; Xavier Caubit [Australie] ; Michael R. Stratton [France] ; James D. Brenton [Royaume-Uni] ; Peter J. Campbell [Royaume-Uni] ; P. Andrew Futreal [Royaume-Uni] ; David Dl Bowtell [Royaume-Uni, Australie]Source :
- Journal of pathology : (Print) [ 0022-3417 ] ; 2012.
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- Pascal (Inist)
- Wicri :
- topic : Génétique.
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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.
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Lau</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></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 wicri:level="1"><inist:fA14 i1="04"><s1>Cancer Research UK Cambridge Research Institute</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>3 aut.</sZ><sZ>12 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cancer Research UK Cambridge Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Raine, Keiran" sort="Raine, Keiran" uniqKey="Raine K" first="Keiran" last="Raine">Keiran Raine</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Teague, Jon" sort="Teague, Jon" uniqKey="Teague J" first="Jon" last="Teague">Jon Teague</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></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 wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Caubit, Xavier" sort="Caubit, Xavier" uniqKey="Caubit X" first="Xavier" last="Caubit">Xavier Caubit</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></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 wicri:level="4"><inist:fA14 i1="07"><s1>Developmental Biology Institute of Marseille-Luminy (IBDML), UMR 6216, CNRS-Inserm-Université de la Méditerranée</s1><s3>FRA</s3><sZ>17 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>CNRS-Inserm-Université de la Méditerranée</wicri:noRegion><placeName><settlement type="city">Marseille</settlement><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region></placeName><orgName type="university">Université de la Méditerranée</orgName><orgName type="institution" wicri:auto="newGroup">Aix-Marseille Université</orgName></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 wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></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 wicri:level="1"><inist:fA14 i1="04"><s1>Cancer Research UK Cambridge Research Institute</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>3 aut.</sZ><sZ>12 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cancer Research UK Cambridge Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Andrew Futreal, P" sort="Andrew Futreal, P" uniqKey="Andrew Futreal P" first="P." last="Andrew Futreal">P. Andrew Futreal</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></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 wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="08"><s1>Sir Peter MacCallum Department of Oncology, University of Melbourne</s1><s3>AUS</s3><sZ>21 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">12-0298756</idno><date when="2012">2012</date><idno type="stanalyst">PASCAL 12-0298756 INIST</idno><idno type="RBID">Pascal:12-0298756</idno><idno type="wicri:Area/PascalFrancis/Corpus">001233</idno><idno type="wicri:Area/PascalFrancis/Curation">004C84</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000D10</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000D10</idno><idno type="wicri:doubleKey">0022-3417:2012:Mcbride D:tandem:duplication:of</idno><idno type="wicri:Area/Main/Merge">005B45</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes</title><author><name sortKey="Mcbride, David J" sort="Mcbride, David J" uniqKey="Mcbride D" first="David J." last="Mcbride">David J. Mcbride</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Etemadmoghadam, Dariush" sort="Etemadmoghadam, Dariush" uniqKey="Etemadmoghadam D" first="Dariush" last="Etemadmoghadam">Dariush Etemadmoghadam</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Pathology, University of Melbourne</s1><s3>AUS</s3><sZ>2 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></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 wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Cancer Research UK Cambridge Research Institute</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>3 aut.</sZ><sZ>12 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cancer Research UK Cambridge Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Alsop, Kathryn" sort="Alsop, Kathryn" uniqKey="Alsop K" first="Kathryn" last="Alsop">Kathryn Alsop</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Department or Biochemistry and Molecular Biology, University of Melbourne</s1><s2>Parkville</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="George, Joshy" sort="George, Joshy" uniqKey="George J" first="Joshy" last="George">Joshy George</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Department or Biochemistry and Molecular Biology, University of Melbourne</s1><s2>Parkville</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Butler, Adam" sort="Butler, Adam" uniqKey="Butler A" first="Adam" last="Butler">Adam Butler</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Cho, Juok" sort="Cho, Juok" uniqKey="Cho J" first="Juok" last="Cho">Juok Cho</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Galappaththige, Danushka" sort="Galappaththige, Danushka" uniqKey="Galappaththige D" first="Danushka" last="Galappaththige">Danushka Galappaththige</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Greenman, Chris" sort="Greenman, Chris" uniqKey="Greenman C" first="Chris" last="Greenman">Chris Greenman</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></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 wicri:level="4"><inist:fA14 i1="06"><s1>Hutchison/MRC Research Centre and Department of Pathology, University of Cambridge</s1><s3>GBR</s3><sZ>10 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName><orgName type="university">Université de Cambridge</orgName></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 wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></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 wicri:level="1"><inist:fA14 i1="04"><s1>Cancer Research UK Cambridge Research Institute</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>3 aut.</sZ><sZ>12 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cancer Research UK Cambridge Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Raine, Keiran" sort="Raine, Keiran" uniqKey="Raine K" first="Keiran" last="Raine">Keiran Raine</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Teague, Jon" sort="Teague, Jon" uniqKey="Teague J" first="Jon" last="Teague">Jon Teague</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></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 wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Caubit, Xavier" sort="Caubit, Xavier" uniqKey="Caubit X" first="Xavier" last="Caubit">Xavier Caubit</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Cancer Genomics and Genetics, Peter MacCallum Cancer Centre</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></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 wicri:level="4"><inist:fA14 i1="07"><s1>Developmental Biology Institute of Marseille-Luminy (IBDML), UMR 6216, CNRS-Inserm-Université de la Méditerranée</s1><s3>FRA</s3><sZ>17 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>CNRS-Inserm-Université de la Méditerranée</wicri:noRegion><placeName><settlement type="city">Marseille</settlement><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region></placeName><orgName type="university">Université de la Méditerranée</orgName><orgName type="institution" wicri:auto="newGroup">Aix-Marseille Université</orgName></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 wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></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 wicri:level="1"><inist:fA14 i1="04"><s1>Cancer Research UK Cambridge Research Institute</s1><s2>Cambridge</s2><s3>GBR</s3><sZ>3 aut.</sZ><sZ>12 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Cancer Research UK Cambridge Research Institute</wicri:noRegion></affiliation></author><author><name sortKey="Andrew Futreal, P" sort="Andrew Futreal, P" uniqKey="Andrew Futreal P" first="P." last="Andrew Futreal">P. Andrew Futreal</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></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 wicri:level="1"><inist:fA14 i1="01"><s1>Cancer Genome Project, Wellcome Trust Sanger Institute</s1><s2>Hinxton, Cambridge</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>13 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>18 aut.</sZ><sZ>20 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Royaume-Uni</country><wicri:noRegion>Hinxton, Cambridge</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="08"><s1>Sir Peter MacCallum Department of Oncology, University of Melbourne</s1><s3>AUS</s3><sZ>21 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author></analytic><series><title level="j" type="main">Journal of pathology : (Print)</title><title level="j" type="abbreviated">J. pathol. : (Print)</title><idno type="ISSN">0022-3417</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of pathology : (Print)</title><title level="j" type="abbreviated">J. pathol. : (Print)</title><idno type="ISSN">0022-3417</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Anatomic pathology</term><term>Breast cancer</term><term>Chromosome</term><term>Gene rearrangement</term><term>Genetics</term><term>Genome</term><term>Ovary cancer</term><term>Tandemly repeated sequence</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Cancer de l'ovaire</term><term>Séquence répétée en tandem</term><term>Chromosome</term><term>Cancer du sein</term><term>Génétique</term><term>Génome</term><term>Réarrangement génique</term><term>Anatomopathologie</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Génétique</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.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Angleterre de l'Est</li><li>Provence-Alpes-Côte d'Azur</li><li>Victoria (État)</li></region><settlement><li>Cambridge</li><li>Marseille</li><li>Melbourne</li></settlement><orgName><li>Aix-Marseille Université</li><li>Université de Cambridge</li><li>Université de Melbourne</li><li>Université de la Méditerranée</li></orgName></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Mcbride, David J" sort="Mcbride, David J" uniqKey="Mcbride D" first="David J." last="Mcbride">David J. Mcbride</name></noRegion><name sortKey="Andrew Futreal, P" sort="Andrew Futreal, P" uniqKey="Andrew Futreal P" first="P." last="Andrew Futreal">P. Andrew Futreal</name><name sortKey="Bowtell, David Dl" sort="Bowtell, David Dl" uniqKey="Bowtell D" first="David Dl" last="Bowtell">David Dl Bowtell</name><name sortKey="Brenton, James D" sort="Brenton, James D" uniqKey="Brenton J" first="James D." last="Brenton">James D. Brenton</name><name sortKey="Butler, Adam" sort="Butler, Adam" uniqKey="Butler A" first="Adam" last="Butler">Adam Butler</name><name sortKey="Campbell, Peter J" sort="Campbell, Peter J" uniqKey="Campbell P" first="Peter J." last="Campbell">Peter J. Campbell</name><name sortKey="Cho, Juok" sort="Cho, Juok" uniqKey="Cho J" first="Juok" last="Cho">Juok Cho</name><name sortKey="Cooke, Susanna L" sort="Cooke, Susanna L" uniqKey="Cooke S" first="Susanna L." last="Cooke">Susanna L. Cooke</name><name sortKey="Cooke, Susanna L" sort="Cooke, Susanna L" uniqKey="Cooke S" first="Susanna L." last="Cooke">Susanna L. Cooke</name><name sortKey="Galappaththige, Danushka" sort="Galappaththige, Danushka" uniqKey="Galappaththige D" first="Danushka" last="Galappaththige">Danushka Galappaththige</name><name sortKey="Greenman, Chris" sort="Greenman, Chris" uniqKey="Greenman C" first="Chris" last="Greenman">Chris Greenman</name><name sortKey="Howarth, Karen D" sort="Howarth, Karen D" uniqKey="Howarth K" first="Karen D." last="Howarth">Karen D. Howarth</name><name sortKey="Lau, King W" sort="Lau, King W" uniqKey="Lau K" first="King W." last="Lau">King W. Lau</name><name sortKey="Ng, Charlotte K" sort="Ng, Charlotte K" uniqKey="Ng C" first="Charlotte K." last="Ng">Charlotte K. Ng</name><name sortKey="Raine, Keiran" sort="Raine, Keiran" uniqKey="Raine K" first="Keiran" last="Raine">Keiran Raine</name><name sortKey="Teague, Jon" sort="Teague, Jon" uniqKey="Teague J" first="Jon" last="Teague">Jon Teague</name><name sortKey="Wedge, David C" sort="Wedge, David C" uniqKey="Wedge D" first="David C." last="Wedge">David C. Wedge</name></country><country name="Australie"><region name="Victoria (État)"><name sortKey="Etemadmoghadam, Dariush" sort="Etemadmoghadam, Dariush" uniqKey="Etemadmoghadam D" first="Dariush" last="Etemadmoghadam">Dariush Etemadmoghadam</name></region><name sortKey="Alsop, Kathryn" sort="Alsop, Kathryn" uniqKey="Alsop K" first="Kathryn" last="Alsop">Kathryn Alsop</name><name sortKey="Alsop, Kathryn" sort="Alsop, Kathryn" uniqKey="Alsop K" first="Kathryn" last="Alsop">Kathryn Alsop</name><name sortKey="Bowtell, David Dl" sort="Bowtell, David Dl" uniqKey="Bowtell D" first="David Dl" last="Bowtell">David Dl Bowtell</name><name sortKey="Caubit, Xavier" sort="Caubit, Xavier" uniqKey="Caubit X" first="Xavier" last="Caubit">Xavier Caubit</name><name sortKey="Etemadmoghadam, Dariush" sort="Etemadmoghadam, Dariush" uniqKey="Etemadmoghadam D" first="Dariush" last="Etemadmoghadam">Dariush Etemadmoghadam</name><name sortKey="George, Joshy" sort="George, Joshy" uniqKey="George J" first="Joshy" last="George">Joshy George</name><name sortKey="George, Joshy" sort="George, Joshy" uniqKey="George J" first="Joshy" last="George">Joshy George</name></country><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Stratton, Michael R" sort="Stratton, Michael R" uniqKey="Stratton M" first="Michael R." last="Stratton">Michael R. Stratton</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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