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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 ; 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

Nature (London), 2015-05, Vol.521 (7553), p.489-494 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
Whole-genome characterization of chemoresistant ovarian cancer
Autor: 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 ; 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
Assuntos: Analysis ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics ; Care and treatment ; Chromosomes ; Cohort Studies ; Cyclin E - genetics ; Cystadenocarcinoma, Serous - drug therapy ; Cystadenocarcinoma, Serous - genetics ; DNA Methylation ; DNA Mutational Analysis ; DNA sequencing ; DNA-Binding Proteins - genetics ; Drug Resistance, Neoplasm - drug effects ; Drug Resistance, Neoplasm - genetics ; Female ; Gene amplification ; Gene expression ; Genes, BRCA1 ; Genes, BRCA2 ; Genes, Neurofibromatosis 1 ; Genetic aspects ; Genome, Human - genetics ; Genomes ; Germ-Line Mutation - genetics ; Humans ; Metastasis ; Methylation ; Mutagenesis - genetics ; Mutation ; Nucleotide sequencing ; Oncogene Proteins - genetics ; Ovarian cancer ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - genetics ; Patients ; Promoter Regions, Genetic - genetics ; PTEN Phosphohydrolase - genetics ; Retinoblastoma Protein - genetics ; Tumors
É parte de: Nature (London), 2015-05, Vol.521 (7553), p.489-494
Descrição: 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.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Whole-genome characterization of chemoresistant ovarian cancer

England: Nature Publishing Group

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