Transcriptomics

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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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