Imperial College London
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DR JAMES M. FLANAGAN

Faculty of Medicine, Department of Surgery & Cancer

Reader in Epigenetics
 
 
 
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Contact

 

+44 (0)20 7594 2127j.flanagan

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gallon:2021:10.1186/s13148-021-01105-6,
author = {Gallon, J and Curry, E and Loomis, E and Martin, N and Brody, L and Garner, I and Brown, R and Flanagan, J},
doi = {10.1186/s13148-021-01105-6},
journal = {Clinical Epigenetics},
pages = {1--15},
title = {Chromatin accessibility changes at intergenic regions associate with ovarian cancer drug resistance},
url = {http://dx.doi.org/10.1186/s13148-021-01105-6},
volume = {13},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundResistance to DNA damaging chemotherapies leads to cancer treatment failure and poor patient prognosis. We investigated how genomic distribution of accessible chromatin sites is altered during acquisition of cisplatin resistance using matched ovarian cell lines from high grade serous ovarian cancer (HGSOC) patients before and after becoming clinically resistant to platinum-based chemotherapy.ResultsResistant lines show altered chromatin accessibility at intergenic regions, but less so at gene promoters. Clusters of cis-regulatory elements at these intergenic regions show chromatin changes that are associated with altered expression of linked genes, with enrichment for genes involved in the Fanconi anemia/BRCA DNA damage response pathway. Further, genome-wide distribution of platinum adducts associates with the chromatin changes observed and distinguish sensitive from resistant lines. In the resistant line, we observe fewer adducts around gene promoters and more adducts at intergenic regions.ConclusionsChromatin changes at intergenic regulators of gene expression are associated with in vivo derived drug resistance and Pt-adduct distribution in patient-derived HGSOC drug resistance models.
AU  - Gallon,J
AU  - Curry,E
AU  - Loomis,E
AU  - Martin,N
AU  - Brody,L
AU  - Garner,I
AU  - Brown,R
AU  - Flanagan,J
DO  - 10.1186/s13148-021-01105-6
EP  - 15
PY  - 2021///
SN  - 1868-7083
SP  - 1
TI  - Chromatin accessibility changes at intergenic regions associate with ovarian cancer drug resistance
T2  - Clinical Epigenetics
UR  - http://dx.doi.org/10.1186/s13148-021-01105-6
UR  - https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-021-01105-6
UR  - http://hdl.handle.net/10044/1/89728
VL  - 13
ER  -
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