Whole genome characterisation of chemoresistant ovarian cancer [Illumina_450K_Methylation]

·发布 May 19, 2015 ·更新 May 24, 2015

121

样本数

121

实验数

芯片平台

实验描述

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

芯片平台

A-GEOD-13534

Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482_v.1.1)（121 例）

样本属性

cell type

high grade serous ovarian cancer, normal

organism

Homo sapiens

organism part

ascites, fallopian tube, PrimaryTumour, Primarytumour, TumourLocalRecurrence, TumourMetastasisToDistantLocation, Tumourmetastasistodistantlocation

sex

female

实验信息

登记号

E-GEOD-65820

GEO 编号

GSE65820

实验类型

methylation profiling by array

物种

Homo sapiens

发布日期

May 19, 2015

更新日期

May 24, 2015

提交者

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

外部链接

ArrayExpress 原始页 NCBI GEO：GSE65820

分析服务

Whole genome characterisation of chemoresistant ovarian cancer [Illumina_450K_Methylation]

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