Integrated genomic analyses of ovarian carcinoma

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Title: Integrated genomic analyses of ovarian carcinoma
Authors: Bell, D
Berchuck, A
Birrer, M
Chien, J
Cramer, DW
Dao, F
Dhir, R
DiSaia, P
Gabra, H
Glenn, P
Godwin, AK
Triche, T
Berman, BP
Van den Berg, DJ
Buckley, J
Baylin, SB
Zhang, J
Spellman, PT
Purdom, E
Iacocca, M
Shelton, T
Voet, D
Neuvial, P
Bengtsson, H
Jakkula, LR
Durinck, S
Han, J
Dorton, S
Marr, H
Zhang, H
Choi, YG
Wang, V
Wilkinson, J
Nguyen, H
Wang, NJ
Imielinski, M
Ngai, J
Conboy, JG
Parvin, B
Feiler, HS
Speed, TP
Gray, JW
Wu, CJ
Bloom, T
Levine, DA
Li, L
Socci, ND
Liang, Y
Taylor, BS
Kalloger, S
Schultz, N
Borsu, L
Lash, AE
Brennan, C
Ardlie, K
Viale, A
Shukla, S
Grimm, D
Sander, C
Ladanyi, M
Hoadley, KA
Meng, S
Du, Y
Karlan, BY
Shi, Y
Fennell, T
Cibulskis, K
Lawrence, MS
Meyerson, M
Hatfield, M
Mills, GB
Sivachenko, A
Jing, R
Park, RW
Liu, Y
Park, PJ
Ramos, AH
Noble, M
Chin, L
Carter, H
Kim, D
Morris, S
Winckler, W
Karchin, R
Morrison, C
Spellman, PT
Purdom, E
Baldwin, J
Neuvial, P
Bengtsson, H
Durinck, S
Han, J
Korkola, JE
Yena, P
Heiser, LM
Getz, G
Cho, RJ
Hu, Z
Gabriel, S
Mutch, D
Parvin, B
Speed, TP
Gray, JW
Schultz, N
Cerami, E
Rhodes, P
Taylor, BS
Olshen, A
Verhaak, RGW
Lander, ES
Reva, B
Antipin, Y
Shen, R
Olvera, N
Mankoo, P
Sheridan, R
Ciriello, G
Sherman, M
Chang, WK
Bernanke, JA
Hayes, DN
Borsu, L
Carter, SL
Levine, DA
Ladanyi, M
Sander, C
Haussler, D
Orsulic, S
Benz, CC
Paulauskis, J
Stuart, JM
Zhang, N
Benz, SC
Sanborn, JZ
Vaske, CJ
Mermel, CH
Zhu, J
Szeto, C
Scott, GK
Yau, C
Hoadley, KA
Rabeno, B
Ding, L
Park, K
Du, Y
Balu, S
Hayes, DN
Perou, CM
Saksena, G
Wilkerson, MD
Millis, S
Kahn, A
Turman, YJ
Fulton, RS
Onofrio, RC
Greene, JM
Sfeir, R
Jensen, MA
Chen, J
Whitmore, J
Alonso, S
Jordan, J
Chu, A
Rader, JS
Koboldt, DC
Zang, D
Zhang, J
Gross, J
Barker, A
Compton, C
Eley, G
Ferguson, M
Fielding, P
Gerhard, DS
Myles, R
McLellan, MD
Schaefer, C
Helms, EB
Shaw, KRM
Sikic, BI
Lawrence, MS
Vaught, J
Vockley, JB
Good, PJ
Guyer, MS
Ozenberger, B
Wylie, T
Peterson, J
Thomson, E
Balu, S
Smith-McCune, K
Sood, AK
Bowtell, D
Hubbard, D
Penny, R
Testa, JR
Chang, K
Walker, J
Dinh, HH
Drummond, JA
Fowler, G
Zhou, X
Gunaratne, P
Hawes, AC
Kovar, CL
Lewis, LR
Gupta, S
Morgan, MB
O'Laughlin, M
Newsham, IF
Santibanez, J
Reid, JG
Trevino, LR
Wu, J
Wu, Y-Q
Wang, M
Muzny, DM
Wheeler, DA
Gibbs, RA
Ardlie, K
Crenshaw, A
Getz, G
Lawrence, MS
Cibulskis, K
Sivachenko, AY
Topal, MD
Sougnez, C
Dooling, DJ
Fulton, L
Akbani, R
Levine, DA
Abbott, R
Dees, ND
Zhang, Q
Kandoth, C
Wendl, M
Schierding, W
Shen, D
Harris, CC
Chin, L
Baggerly, KA
Schmidt, H
Wilson, RK
Kalicki, J
Delehaunty, KD
Fronick, CC
Demeter, R
Cook, L
Wallis, JW
Lin, L
Magrini, VJ
Yung, WK
Hodges, JS
Protopopov, A
Perou, CM
Eldred, JM
Smith, SM
Pohl, CS
Vandin, F
Raphael, BJ
Weinstock, GM
Mardis, R
Mills, GB
Zhang, J
Kim, TM
Hartmann, L
Getz, G
Perna, I
Xiao, Y
Zhang, H
Ren, G
Sathiamoorthy, N
Park, RW
Petrelli, N
Lee, E
Park, PJ
Kucherlapati, R
Absher, DM
Voet, D
Huang, M
Waite, L
Sherlock, G
Brooks, JD
Li, JZ
Weinstein, JN
Xu, J
Myers, RM
Laird, PW
Cope, L
Herman, JG
Saksena, G
Shen, H
Huntsman, DG
Weisenberger, DJ
Noushmehr, H
Penny, R
Pan, F
Item Type: Journal Article
Abstract: A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients’ lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.
Issue Date: 30-Jun-2011
Date of Acceptance: 27-Apr-2011
URI: http://hdl.handle.net/10044/1/71276
DOI: https://doi.org/10.1038/nature10166
ISSN: 0028-0836
Publisher: Nature Research
Start Page: 609
End Page: 615
Journal / Book Title: Nature
Volume: 474
Issue: 7353
Copyright Statement: ©2012 Macmillan Publishers Limited. All rights reserved
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
HIGH-THROUGHPUT ANNOTATION
GYNECOLOGIC-ONCOLOGY-GROUP
GRADE SEROUS CARCINOMA
BRCA MUTATION CARRIERS
CLEAR-CELL CARCINOMA
SOMATIC MUTATIONS
CANCER STATISTICS
DRIVER MUTATIONS
HYBRID SELECTION
MUTANT-CELLS
Aged
Carcinoma
DNA Methylation
Female
Gene Dosage
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genomics
Humans
MicroRNAs
Middle Aged
Mutation
Ovarian Neoplasms
RNA, Messenger
Cancer Genome Atlas Research Network
Humans
Carcinoma
Ovarian Neoplasms
MicroRNAs
RNA, Messenger
Gene Expression Profiling
Genomics
DNA Methylation
Gene Expression Regulation, Neoplastic
Gene Dosage
Mutation
Aged
Middle Aged
Female
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
HIGH-THROUGHPUT ANNOTATION
GYNECOLOGIC-ONCOLOGY-GROUP
GRADE SEROUS CARCINOMA
BRCA MUTATION CARRIERS
CLEAR-CELL CARCINOMA
SOMATIC MUTATIONS
CANCER STATISTICS
DRIVER MUTATIONS
HYBRID SELECTION
MUTANT-CELLS
General Science & Technology
MD Multidisciplinary
Publication Status: Published
Online Publication Date: 2011-06-29
Appears in Collections:Division of Surgery
Division of Cancer



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