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E-GEOD-65819 - Whole genome characterisation of chemoresistant ovarian cancer [NanoString miRNA]

Status
Released on 19 May 2015, last updated on 24 May 2015
Organism
Homo sapiens
Samples (121)
Array (1)
Protocols (5)
Description
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. Total RNA was hybridised to NanoString miRNA Human v2.1 probes, immobilized to NanoString cartridge and analysed on the NanoString Digital Analyzer. NanoString nSolver Analysis Software was utilised to check QC metrics and extract raw miRNA counts. Expression was normalised for input using the housekeeping genes. Contributor: The Australian Ovarian Cancer Study Group
Experiment type
transcription profiling by array 
Contacts
Ann-Marie Patch <ann-marie.patch@qimrberghofer.edu.au>, Andrea Jewell, Andrew Lonie, Angelika N Christ, Anna deFazio, Anne Hamilton, Barsha Poudel, Catherine Kennedy, Charlotte Wilhelm-Benartzi, Chris Mitchell, Collin Stewart, Conrad Leonard, Craig Nourse, Dale W Garsed, Dariush Etemadmoghadam, Darrin F Taylor, David D Bowtell, David K Miller, Ed Curry, Ehsan Nourbakhsh, Elizabeth L Christie, Emma Markham, Ernst Lengyel, Euan Stronach, Felicity Newell, George Au-Yeung, Gisela Mir Arnau, Greg Young, Hani Gabra, Heather Thorne, Huei San, Ivon Harliwong, J L Fink, Jan Pyman, Jason Ellul, Jillian Hung, Jodie Leditschke, John V Pearson, Joshy George, Joy Hendley, Karin S Kassahn, Kate Strachan, Kathryn Alsop, Katia Nones, Kelly Quek, Linda Mileshkin, Maria A Doyle, Mark Shackleton, Matthew Anderson, Michael C Quinn, Michael Friedlander, Michael Quinn, Nadia Traficante, Nathan Hall, Nick Waddell, Nicola Waddell, Oliver Holmes, Orla McNally, Patricia O'Brien, Paul Harnett, Paul Waring, Peter J Bailey, Peter J Wilson, Prue Cowin, Qinying Xu, Ravikiran Vedururu, Richard W Tothill, Robert Brown, Ronny Drapkin, San Leong, Scott Wood, Sean M Grimmond, Senel Idrisoglu, Shivashankar H Nagaraj, Sian Fereday, Stephen Cordner, Stephen Kazakoff, Suzanne Manning, Timothy J Bruxner, Timothy P Holloway, Timothy Semple, Walid Azar, Yoke E Chiew
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-65819.idf.txt
Sample and data relationshipE-GEOD-65819.sdrf.txt
Raw data (1)E-GEOD-65819.raw.1.zip
Processed data (1)E-GEOD-65819.processed.1.zip
Array designA-GEOD-19765.adf.txt
Links