EXPERIMENT_TITLE: GSM6063559: UCD52CR, Hi-C seq; Homo sapiens; Mus musculus; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: Hi-C sequencing was performed according to the expirimental procedure described in Dozmorov MG. Et al. Methods 2021 (PMID: 33880552). Libraries were constructed according to the protocol described in Dozmorov MG. Et al. Methods 2021 (PMID: 33880552).
STUDY_DESCRIPTOR_STUDY_ABSTRACT: 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: Hi-C sequencing analysis performed on two replicates for each of the two phenotypes (primary tumor and carboplatin-resistant state).
SAMPLE_TITLE: UCD52CR, Hi-C seq
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "Basal-like triple-negative breast cancer patient-derived xenograft; UCD52"}, {"TAG": "cell line", "VALUE": "Basal-like triple-negative breast cancer patient-derived xenograft; UCD52"}, {"TAG": "cell type", "VALUE": "carboplatin resistant tumor from UCD52 PDX model"}, {"TAG": "treatment", "VALUE": "carboplatin"}]
Pool_Member_@attributes_sample_title: UCD52CR, Hi-C seq
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