Imperial College London
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ProfessorBobBrown

Faculty of Medicine, Department of Surgery & Cancer

Senior Research Investigator
 
 
 
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Contact

 

+44 (0)20 7594 1804b.brown Website

 
 
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Assistant

 

Ms Sophie Lions +44 (0)20 7594 2792

 
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Location

 

1 007Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gallon:2021:10.1101/2021.02.24.432641,
author = {Gallon, J and Loomis, E and Curry, E and Martin, N and Brody, L and Garner, I and Brown, R and Flanagan, JM},
doi = {10.1101/2021.02.24.432641},
journal = {Clinical Epigenetics},
title = {Chromatin accessibility changes at intergenic regions associates with ovarian cancer drug resistance},
url = {http://dx.doi.org/10.1101/2021.02.24.432641},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p>We have investigated how genomic distribution of chromatin accessibilities alter during acquisition of resistance to carboplatin-based chemotherapy using matched ovarian cell lines from high grade serous ovarian cancer (HGSOC) patients before and after becoming clinically resistant to platinum-based chemotherapy. Resistant lines show altered chromatin accessibility at intergenic regions, but less so at gene promoters. Super-enhancers, as defined by 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. Thus, chromatin changes at intergenic regulators of gene expression are associated with <jats:italic>in vivo</jats:italic> derived drug resistance and Pt-adduct distribution in patient-derived HGSOC drug resistance models.</jats:p>
AU  - Gallon,J
AU  - Loomis,E
AU  - Curry,E
AU  - Martin,N
AU  - Brody,L
AU  - Garner,I
AU  - Brown,R
AU  - Flanagan,JM
DO  - 10.1101/2021.02.24.432641
PY  - 2021///
SN  - 1868-7083
TI  - Chromatin accessibility changes at intergenic regions associates with ovarian cancer drug resistance
T2  - Clinical Epigenetics
UR  - http://dx.doi.org/10.1101/2021.02.24.432641
ER  -
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