Dataset Information


Whole genome characterisation of chemoresistant ovarian cancer [Illumina_450K_Methylation]

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. Genomic DNA (500ng) was bisulfite converted using EZ DNA methylation Kit (Zimo Research) following the manufacturer’s protocol with modification for Illumina Infinium Methyaltion arrays. Samples were hybridized to Infinium Human Methylation 450K BeadChips (Illumina) according to the manufacturer’s protocol. Arrays were scanned on Iscan (Illumina). Data was background corrected, normalized to internal controls and QC was performed at the probe and sample level. COMBAT was used to remove batch effects (Johnson et al., 2007). Contributor: The Australian Ovarian Cancer Study Group

ORGANISM(S): Homo sapiens  

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

PROVIDER: E-GEOD-65820 | ArrayExpress | 2015-05-19



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