Transcriptomics

Dataset Information

6

Whole genome characterisation of chemoresistant ovarian cancer [NanoString miRNA]


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. 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

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  Ravikiran Vedururu  Huei San  Felicity Newell  Timothy J Bruxner  Matthew Anderson  Michael C Quinn  Scott Wood  Barsha Poudel  Qinying Xu  Karin S Kassahn  Ernst Lengyel  Emma Markham  Catherine Kennedy  George Au-Yeung  Robert Brown  Jodie Leditschke  Timothy P Holloway  Stephen Kazakoff  Shivashankar H Nagaraj  Nicola Waddell  San Leong  Peter J Wilson  Kelly Quek  Dale W Garsed  David K Miller  Dariush Etemadmoghadam  Andrea Jewell  Paul Harnett  J L Fink  Hani Gabra  Mark Shackleton  Stephen Cordner  David D Bowtell  Peter J Bailey  Heather Thorne  Yoke E Chiew  Linda Mileshkin  John V Pearson  Anne Hamilton  Prue Cowin  Darrin F Taylor  Charlotte Wilhelm-Benartzi  Richard W Tothill  Nathan Hall  Conrad Leonard  Ehsan Nourbakhsh  Nick Waddell  Andrew Lonie  Ann-Marie Patch  Katia Nones  Gisela Mir Arnau  Ed Curry  Ronny Drapkin  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  Nadia Traficante  Jillian Hung  Maria A Doyle  Oliver Holmes  Timothy Semple 

PROVIDER: E-GEOD-65819 | ArrayExpress | 2015-05-19

SECONDARY ACCESSION(S): GSE65819PRJNA275138

REPOSITORIES: GEO, ArrayExpress

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