Whole-genome characterization of chemoresistant ovarian cancer

Patch, Ann-Marie, Christie, Elizabeth L., Etemadmoghadam, Dariush, Garsed, Dale W., George, Joshy, Fereday, Sian, Nones, Katia, Cowin, Prue, Alsop, Kathryn, Bailey, Peter J., Kassahn, Karin S., Newell, Felicity, Quinn, Michael C. J., Kazakoff, Stephen, Quek, Kelly, Wilhelm-Benartzi, Charlotte, Curry, Ed, Leong, Huei San, The Australian Ovarian Cancer Study Group, Hamilton, Anne, Mileshkin, Linda, Au-Yeung, George, Kennedy, Catherine, Hung, Jillian, Chiew, Yoke-Eng, Harnett, Paul, Friedlander, Michael, Quinn, Michael, Pyman, Jan, Cordner, Stephen, O'Brien, Patricia, Leditschke, , Jodie, Young, Greg, Strachan, Kate, Waring, Paul, Azar, Walid, Mitchell, Chris, Traficante, Nadia, Hendley, Joy, Thorne, Heather, Shackleton, Mark, Miller, David K., Arnau, Gisela Mir, Tothill, Richard W., Holloway, Timothy P., Semple, Timothy, Harliwong, Ivon, Nourse, Craig, Nourbakhsh, Ehsan, Manning, Suzanne, Idrisoglu, Senel, Bruxner, Timothy J. C., Christ, Angelika N., Poudel, Barsha, Holmes, Oliver, Anderson, Matthew, Leonard, Conrad, Lonie, Andrew, Hall, Nathan, Wood, Scott, Taylor, Darrin F., Xu, Qinying, Fink, J. Lynn, Waddell, Nick, Drapkin, Ronny, Stronach, Euan, Gabra, Hani, Brown, Robert, Jewell, Andrea, Nagaraj, Shivashankar H., Markham, Emma, Wilson, Peter J., Ellul, Jason, McNally, Orla, Doyle, Maria A., Vedururu, Ravikiran, Stewart, Collin, Lengyel, Ernst, Pearson, John V., Waddell, Nicola, Defazio, Anna, Grimmond, Sean M. and Bowtell, David D. L. (2015) Whole-genome characterization of chemoresistant ovarian cancer. Nature, 521 7553: 489-494. doi:10.1038/nature14410

Author Patch, Ann-Marie
Christie, Elizabeth L.
Etemadmoghadam, Dariush
Garsed, Dale W.
George, Joshy
Fereday, Sian
Nones, Katia
Cowin, Prue
Alsop, Kathryn
Bailey, Peter J.
Kassahn, Karin S.
Newell, Felicity
Quinn, Michael C. J.
Kazakoff, Stephen
Quek, Kelly
Wilhelm-Benartzi, Charlotte
Curry, Ed
Leong, Huei San
The Australian Ovarian Cancer Study Group
Hamilton, Anne
Mileshkin, Linda
Au-Yeung, George
Kennedy, Catherine
Hung, Jillian
Chiew, Yoke-Eng
Harnett, Paul
Friedlander, Michael
Quinn, Michael
Pyman, Jan
Cordner, Stephen
O'Brien, Patricia
Leditschke, , Jodie
Young, Greg
Strachan, Kate
Waring, Paul
Azar, Walid
Mitchell, Chris
Traficante, Nadia
Hendley, Joy
Thorne, Heather
Shackleton, Mark
Miller, David K.
Arnau, Gisela Mir
Tothill, Richard W.
Holloway, Timothy P.
Semple, Timothy
Harliwong, Ivon
Nourse, Craig
Nourbakhsh, Ehsan
Manning, Suzanne
Idrisoglu, Senel
Bruxner, Timothy J. C.
Christ, Angelika N.
Poudel, Barsha
Holmes, Oliver
Anderson, Matthew
Leonard, Conrad
Lonie, Andrew
Hall, Nathan
Wood, Scott
Taylor, Darrin F.
Xu, Qinying
Fink, J. Lynn
Waddell, Nick
Drapkin, Ronny
Stronach, Euan
Gabra, Hani
Brown, Robert
Jewell, Andrea
Nagaraj, Shivashankar H.
Markham, Emma
Wilson, Peter J.
Ellul, Jason
McNally, Orla
Doyle, Maria A.
Vedururu, Ravikiran
Stewart, Collin
Lengyel, Ernst
Pearson, John V.
Waddell, Nicola
Defazio, Anna
Grimmond, Sean M.
Bowtell, David D. L.
Title Whole-genome characterization of chemoresistant ovarian cancer
Journal name Nature   Check publisher's open access policy
ISSN 1476-4687
Publication date 2015-05-28
Year available 2015
Sub-type Article (original research)
DOI 10.1038/nature14410
Open Access Status Not yet assessed
Volume 521
Issue 7553
Start page 489
End page 494
Total pages 6
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1000 General
Abstract Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1.
Keyword High-grade serous ovarian cancer
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 11-0748
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
UQ Diamantina Institute Publications
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