GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE201434 Query DataSets for GSE201434
Status Public on Apr 06, 2023
Title Carboplatin resistance-associated changes in the 3D chromatin landscape of a triple-negative breast cancer Patient-Derived Xenograft [RNA-Seq]
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Changes in the three-dimensional (3D) structure of the genome are an emerging hallmark of cancer. However, little is known about the rewiring of the 3D chromatin landscape during cancer progression to a chemotherapy-resistant state. We utilized a patient-derived xenograft (PDX) mouse model of triple-negative breast cancer (UCD52) to characterize changes in the 3D structure between the primary tumor and carboplatin-resistant state. Systematic integration of matched chromatin conformation capture (Hi-C), RNA-seq, and whole-genome sequencing data revealed a widespread increase in short-range (<2Mb) interactions with the corresponding increase in chromatin looping and topologically associating domain (TAD) formation, chromatin state switching into a more active state, large-scale deletions, amplification of ATP-binding cassette (ABC) transporters and nearly complete shutdown of drug metabolism pathways. Rewiring of the 3D genome was associated with TP53, TP63, BATF, FOS-JUN family of transcription factors and led to activation of many aggressiveness-, metastasis- and other cancer-related pathways. Transcriptome changes suggest the role of downregulated protein-coding genes and upregulated long-noncoding RNAs in drug resistance. Integrative analysis confirmed increased ribosome biogenesis and oxidative phosphorylation, suggesting the role of mitochondrial metabolic processes. Our results highlight that 3D genome remodeling may be a key mechanism underlying drug resistance.
Overall design RNA-sequencing analysis performed on three replicates for each of the two phenotypes (primary tumor and carboplatin-resistant state).
Contributor(s) Dozmorov MG, Marshall MA, Rashid N, Grible J, Olex AL, Murthy K, Chakraborty A, Reyna J, Salgado Figueroa D, Da-Inn Lee E, Baur B, Roy S, Ay F, Harrell C
Citation(s) 37012431, 37160896
Submission date Apr 25, 2022
Last update date Aug 04, 2023
Contact name Mikhail Dozmorov
Organization name Virginia Commonwealth University
Department Biostatistics
Street address 830 E Main St
City Richmond
State/province VA
ZIP/Postal code 23298
Country USA
Platforms (1)
GPL22245 Illumina HiSeq 2500 (Homo sapiens; Mus musculus)
Samples (6)
GSM6063612 UCD52PR, replicate 1, RNAseq
GSM6063613 UCD52PR, replicate 2, RNAseq
GSM6063614 UCD52PR, replicate 3, RNAseq
This SubSeries is part of SuperSeries:
GSE201435 Carboplatin resistance-associated changes in the 3D chromatin landscape of a triple-negative breast cancer Patient-Derived Xenograft
BioProject PRJNA831784

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE201434_RAW.tar 22.5 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap