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Series GSE65820 Query DataSets for GSE65820
Status Public on May 19, 2015
Title Whole genome characterisation of chemoresistant ovarian cancer [Illumina_450K_Methylation]
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary 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.
 
Overall design 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
 
Contributor(s) Patch AM, Christie EL, Etemadmoghadam D, Garsed DW, George J, Fereday S, Nones K, Cowin P, Alsop K, Bailey PJ, Kassahn KS, Newell F, Quinn MC, Kazakoff S, Quek K, Wilhelm-Benartzi C, Curry E, San H, Leong S, Hamilton A, Mileshkin L, Au-Yeung G, Kennedy C, Hung J, Chiew YE, Harnett P, Friedlander M, Quinn M, Pyman J, Cordner S, O'Brien P, Leditschke J, Young G, Strachan K, Waring P, Azar W, Mitchell C, Traficante N, Hendley J, Thorne H, Shackleton M, Miller DK, Mir Arnau G, Tothill RW, Holloway TP, Semple T, Harliwong I, Nourse C, Nourbakhsh E, Manning S, Idrisoglu S, Bruxner TJ, Christ AN, Poudel B, Holmes O, Anderson M, Leonard C, Lonie A, Hall N, Wood S, Taylor DF, Xu Q, Fink JL, Waddell N, Drapkin R, Stronach E, Gabra H, Brown R, Jewell A, Nagaraj SH, Markham E, Wilson PJ, Ellul J, McNally O, Doyle MA, Vedururu R, Stewart C, Lengyel E, Pearson JV, Waddell N, deFazio A, Grimmond SM, Bowtell DD
Citation(s) 26017449
Submission date Feb 10, 2015
Last update date Nov 09, 2022
Contact name Ann-Marie Patch
E-mail(s) ann-marie.patch@qimrberghofer.edu.au
Organization name QIMR Berghofer Medical Research Institute
Street address 300 Herston Road
City Herston
State/province QLD
ZIP/Postal code 4006
Country Australia
 
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (121)
GSM1606855 AOCS_001_ICGC_DBPC_20130205_002
GSM1606856 AOCS_004_ICGC_DBPC_20130205_004
GSM1606857 AOCS_005_ICGC_DBPC_20130205_006
This SubSeries is part of SuperSeries:
GSE65821 Whole genome characterisation of chemoresistant ovarian cancer
Relations
BioProject PRJNA275137

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE65820_RAW.tar 1.1 Gb (http)(custom) TAR (of IDAT)
Processed data included within Sample table

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