EXPERIMENT_TITLE: GSM7881296: MCF10A, rep1; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: HiC Libraries were prepared in duplicates for each cell type using the Arima-HiC+ kit (Arima Genomics, USA) according to manufacturer instructions. For each cell line (10A, T1, C1) 1 million cells were used per HiC reaction. Cells were fixed with 1.2% formaldehyde for 12 min. All subsequent steps were carried out according to the Arima protocol. Resulting libraries were amplified with 5 PCR cycles and sequenced on an Illumina NovaSeq 6000 instrument in paired-end run with 2 x101 bp.
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Breast cancer progression entails intricate, multi-level alterations in genome organization and expression. To gain insights into the modifications in chromatin's three-dimensional (3D) structure during breast cancer progression, we conducted an analysis combining Hi-C data with lamina-associated domains (LADs), epigenomic marks, and gene expression in an in vitro model of breast cancer progression. Our results reveal that while the fundamental properties of topologically associating domains (TADs) remain largely stable, significant changes occur in the organization of compartments and subcompartments. These changes are closely correlated with alterations in the expression of oncogenic genes. We also observed a restructuring of TAD-TAD interactions, coinciding with a loss of spatial compartmentalization and radial positioning of the 3D genome. Notably, we identified a previously unrecognized interchromosomal insertion event, wherein a locus on chromosome 8 housing the MYC oncogene becomes inserted into a highly active region on chromosome 10. This insertion event leads to the formation of de novo enhancer contacts and activation of the oncogene, illustrating how structural variants can interact with the 3D genome to drive oncogenic states. In summary, our findings provide evidence for the degradation of genome organization at multiple scales during breast cancer progression revealing the complex interplay between genomic structure and oncogenic processes. Overall design: We generated Hi-C datasets for MCF10A, MCF10AT1, and MCF10Ca1a cell lines to investigate changes in 3D genome conformation during breast cancer progression. ***Please note that the records have been updated with additional/replacement processed data files on Aug 9, 2024****
SAMPLE_TITLE: MCF10A, rep1
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "mammary gland"}, {"TAG": "tissue", "VALUE": "mammary gland"}, {"TAG": "cell line", "VALUE": "MCF10A"}, {"TAG": "cell type", "VALUE": "epithelial cell"}, {"TAG": "disease", "VALUE": "breast cancer"}, {"TAG": "geo_loc_name", "VALUE": "missing"}, {"TAG": "collection_date", "VALUE": "missing"}]
Pool_Member_@attributes_sample_title: MCF10A, rep1
RUN_SET_RUN_Pool_Member_@attributes_sample_title: MCF10A, rep1
RUN_SET_RUN_SRAFiles_SRAFile: [{"Alternatives": [null, null, null], "@attributes": {"cluster": "public", "filename": "SRR26661492.lite", "url": "https://sra-downloadb.be-md.ncbi.nlm.nih.gov/sos6/sra-pub-zq-40/SRR026/26661/SRR26661492/SRR26661492.lite.1", "size": "53570947591", "date": "2023-11-08 04:33:55", "md5": "d36bb35557dac70dd761a1bf22c145f2", "version": "1", "semantic_name": "SRA Lite", "supertype": "Primary ETL", "sratoolkit": "1"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "SRR26661492", "url": "https://sra-pub-run-odp.s3.amazonaws.com/sra/SRR26661492/SRR26661492", "size": "66377437271", "date": "2023-11-03 01:59:56", "md5": "736f141048d0a7898759b500a5000e3e", "version": "1", "semantic_name": "SRA Normalized", "supertype": "Primary ETL", "sratoolkit": "1"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "HiC_001_MCF10A_WT_R2.fastq.gz", "size": "56151570666", "date": "2023-11-03 01:49:12", "md5": "86bc04faad66124637676fe9fff425f8", "version": "1", "semantic_name": "fastq", "supertype": "Original", "sratoolkit": "0"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "HiC_001_MCF10A_WT_R1.fastq.gz", "size": "54725190290", "date": "2023-11-03 01:45:56", "md5": "a17e627950c7a846f133600e41457d30", "version": "1", "semantic_name": "fastq", "supertype": "Original", "sratoolkit": "0"}}]