Chromatin accessibility changes at intergenic regions are associated with ovarian cancer drug resistance.
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Embargo End Date
ICR Authors
Authors
Gallon, J
Loomis, E
Curry, E
Martin, N
Brody, L
Garner, I
Brown, R
Flanagan, JM
Loomis, E
Curry, E
Martin, N
Brody, L
Garner, I
Brown, R
Flanagan, JM
Document Type
Journal Article
Date
2021-06-05
Date Accepted
2021-05-17
Abstract
BACKGROUND: Resistance 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. RESULTS: Resistant 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. CONCLUSIONS: Chromatin 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.
Citation
Clinical epigenetics, 2021, 13 (1), pp. 122 - ?
Source Title
Publisher
BMC
ISSN
1868-7075
eISSN
1868-7083
Collections
Research Team
Medicine (Brown Epigenetic Therapy)
Medicine (Brown Epigenetic Therapy)
Medicine (Brown Epigenetic Therapy)