EXPERIMENT_TITLE: GSM8523316: HiC data for COLO320-DM cell line, Replicate 2.; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: Hi-C libraries were generated as described previously  following a standard protocol  (Rao, Huntley et al. 2014 PMID: 25497547) Hi-C libraries were generated as described previously  following a standard protocol  (Rao, Huntley et al. 2014 PMID: 25497547)
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Extrachromosomal DNA (ecDNA) is a hallmark of aggressive cancer, contributing to both oncogene amplification and tumor heterogeneity. Here, we used Hi-C, super-resolution imaging, and long-read sequencing to explore the nuclear architecture of MYC-amplified ecDNA in colorectal cancer cells. Intriguingly, we observed frequent spatial proximity between ecDNA and 68 repetitive elements which we called ecDNA-interacting elements or EIEs. To characterize a potential regulatory role of EIEs, we focused on a fragment of the L1M4a1#LINE/L1 which we found to be co-amplified with MYC on ecDNA, gaining enhancer-associated chromatin marks in contrast to its normally silenced state. This EIE, in particular, existed as a naturally occurring structural variant upstream of MYC, gaining oncogenic potential in the transcriptionally permissive ecDNA environment.  This EIE sequence is sufficient to enhance MYC expression and is required for cancer cell fitness. These findings suggest that silent repetitive genomic elements can be reactivated on ecDNA, leading to functional cooption and amplification. Repeat element activation on ecDNA represents a mechanism of accelerated evolution and tumor heterogeneity and may have diagnostic and therapeutic potential. Overall design: To interrogate the conformational state of circular extrachromosomal DNA (ecDNA), we performed Hi-C on COLO 320DM colorectal cancer cells.
SAMPLE_TITLE: HiC data for COLO320-DM cell line, Replicate 2.
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "COLO320-DM"}, {"TAG": "cell line", "VALUE": "COLO320-DM"}, {"TAG": "geo_loc_name", "VALUE": "missing"}, {"TAG": "collection_date", "VALUE": "missing"}]
Pool_Member_@attributes_sample_title: HiC data for COLO320-DM cell line, Replicate 2.
RUN_SET_RUN_Pool_Member_@attributes_sample_title: HiC data for COLO320-DM cell line, Replicate 2.
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