Imperial College London
Portrait Picture

DrEdCurry

Faculty of Medicine, Department of Surgery & Cancer

Honorary Lecturer
 
 
 
//

Contact

 

+44 (0)20 7594 5943e.curry

 
 
//

Location

 

Open PlanInstitute of Reproductive and Developmental BiologyHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Brown:2018:10.1158/0008-5472.CAN-17-1650,
author = {Brown, R and Curry, E and Zeller, C and Masrour, N and Patten, D and Gallon, J and Wilhelm-Benartzi, C and Ghaem-Maghami, S and Bowtell, D},
doi = {10.1158/0008-5472.CAN-17-1650},
journal = {Cancer Research},
pages = {1383--1391},
title = {Genes predisposed to DNA hypermethylation during acquired resistance to chemotherapy are identified in ovarian tumors by bivalent chromatin domains at initial diagnosis},
url = {http://dx.doi.org/10.1158/0008-5472.CAN-17-1650},
volume = {78},
year = {2018}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Bivalent chromatin domains containing both active H3K4me3 and repressive H3K27me3 histone marks define gene sets poised for expression or silencing in differentiating embryonic stem (ES) cells. In cancer cells, aberrantly poised genes may facilitate changes in transcriptional states after exposure to anticancer drugs. In this study, we used ChIP-seq to characterize genome-wide positioning of H3K4me3- and H3K27me3-associated chromatin in primary high-grade serous ovarian carcinomas and in normal ovarian surface and fallopian tube tissue. Gene sets with proximal bivalent marks defined in this manner were evaluated subsequently as signatures of systematic change in DNA methylation and gene expression, comparing pairs of tissue samples taken from patients at primary presentation and relapse following chemotherapy. We found that gene sets harboring bivalent chromatin domains at their promoters in tumor tissue, but not normal epithelia, overlapped with Polycomb-repressive complex target genes as well as transcriptionally silenced genes in normal ovarian and tubal stem cells. The bivalently marked genes we identified in tumors before chemotherapy displayed increased promoter CpG methylation and reduced gene expression at relapse after chemotherapy of ovarian cancer. Overall, our results support the hypothesis that preexisting histone modifications at genes in a poised chromatin state may lead to epigenetic silencing during acquired drug resistance.
AU  - Brown,R
AU  - Curry,E
AU  - Zeller,C
AU  - Masrour,N
AU  - Patten,D
AU  - Gallon,J
AU  - Wilhelm-Benartzi,C
AU  - Ghaem-Maghami,S
AU  - Bowtell,D
DO  - 10.1158/0008-5472.CAN-17-1650
EP  - 1391
PY  - 2018///
SN  - 1538-7445
SP  - 1383
TI  - Genes predisposed to DNA hypermethylation during acquired resistance to chemotherapy are identified in ovarian tumors by bivalent chromatin domains at initial diagnosis
T2  - Cancer Research
UR  - http://dx.doi.org/10.1158/0008-5472.CAN-17-1650
UR  - http://hdl.handle.net/10044/1/55837
VL  - 78
ER  -
Download