Rewiring of the 3D genome during acquisition of carboplatin resistance in a triple-negative breast cancer patient-derived xenograft

Changes in the three-dimensional (3D) structure of the genome are an emerging hallmark of cancer. Cancer-associated copy number variants and single nucleotide polymorphisms promote rewiring of chromatin loops, disruption of topologically associating domains (TADs), active/inactive chromatin state sw...

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Published in:Scientific reports 2023-04, Vol.13 (1), p.5420-17, Article 5420
Main Authors: Dozmorov, Mikhail G., Marshall, Maggie A., Rashid, Narmeen S., Grible, Jacqueline M., Valentine, Aaron, Olex, Amy L., Murthy, Kavita, Chakraborty, Abhijit, Reyna, Joaquin, Figueroa, Daniela Salgado, Hinojosa-Gonzalez, Laura, Da-Inn Lee, Erika, Baur, Brittany A., Roy, Sushmita, Ay, Ferhat, Harrell, J. Chuck
Format: Article
Language:English
Subjects:
631/114
631/67/1347
631/67/69
ATP-binding protein
Breast cancer
Carboplatin
Carboplatin - pharmacology
Carboplatin - therapeutic use
Chemotherapy
Chromatin
Conformation
Copy number
Energy metabolism
Genome
Genomes
Heterografts
Humanities and Social Sciences
Humans
Metastases
Mitochondria
multidisciplinary
Oxidative phosphorylation
Phosphorylation
Science
Science (multidisciplinary)
Single-nucleotide polymorphism
Transcription factors
Transcriptomes
Triple Negative Breast Neoplasms - drug therapy
Triple Negative Breast Neoplasms - genetics
Tumors
Whole genome sequencing
Xenografts
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Summary:Changes in the three-dimensional (3D) structure of the genome are an emerging hallmark of cancer. Cancer-associated copy number variants and single nucleotide polymorphisms promote rewiring of chromatin loops, disruption of topologically associating domains (TADs), active/inactive chromatin state switching, leading to oncogene expression and silencing of tumor suppressors. However, little is known about 3D changes during cancer progression to a chemotherapy-resistant state. We integrated chromatin conformation capture (Hi-C), RNA-seq, and whole-genome sequencing obtained from triple-negative breast cancer patient-derived xenograft primary tumors (UCD52) and carboplatin-resistant samples and found increased short-range (
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-32568-7