ENAGenomicsMultiomicsSection of Sleep Medicine, Department of Pediatrics, The University of Chicagohttps://www.ebi.ac.uk/ena/browser/view/PRJNA260179Mus musculusIntermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA), which has been proposed as the major determinant of processes involving tumor invasion and metastasis. To study whether circulating DNA (cirDNA) in blood plasma reflects the changes that the tumor cells undergo under IH conditions, we used a xenografted murine model. Mice engrafted with TC1 epithelial lung and controls were exposed to IH or room air (RA) conditions. Plasma cirDNA amounts were significantly increased in mice exposed to IH (p<0.05). We found a significant correlation between plasma cirDNA concentration and tumor size, weight and invasiveness (p<0.05). Using a microarray-based approach, we identified 2,094 regions showing significant differential cirDNA modifications. System biology analysis revealed an association with molecular pathways misregulated in cancer progression and with distal and TSS-associated transcription factor binding sites. We detected clusters of highly variable regions in chromosomes 7, 13, 14 and X, which may highlight hotspots for DNA deletions. Single locus displayed high intragroup variation, suggesting cellular heterogeneity within the tissue may be associated to cirDNA release. Our result showed that exposure to IH increases the shedding of cirDNA into circulation, which carries epigenetic modifications that may characterize cell populations within the tumor that preferentially release their DNA upon IH exposure. Overall design: 6 xenografted mouse samples were analyzed by microarray analysis: Mouse exposed to IH (n=3, XenoIH group) and mouse exposed to room air conditions (n=3, XenoRA group)xref:PubMed:25415227xref:PubMed:26484214ENA3.4.22.-, Malignant Neoplasm, intermittent, Laboratory, Neoplasms, exits through, Mus domesticus, Deficiencies, Benign Neoplasm, mouse, mini-ICE, CASP-14, Hypoxia., Tumor, Malignant, DNA fingerprinting, House Mouse, Oxygen Deficiency, Oxygen Deficiencies, Anoxia, Benign, House, Mus, interrupted, Mini-ICE, Neoplasm, Mus musculus domesticus, Mice, Mus musculus, Caspase-14 subunit p10, Malignancy, Swiss, mice, Swiss Mouse, Hypoxemia, Benign Neoplasms, House Mice, Swiss Mice, Caspase-14 subunit p19, Cancers, exposed, MICE, Malignant Neoplasms, Laboratory Mice, domesticus, Neoplasias, Oxygen, extruding from, Deficiency, DNA fingerprint, Malignancies, Mouse, DNA finger printing, Anoxemia, other neoplasm, Laboratory Mouse, Neoplasia, DNA profiling, Cancer, TumorsMus musculus, Laboratory Mice., House, Mus, Laboratory, Swiss, Mus domesticus, mouse, Mus musculus domesticus, Swiss Mouse, mouse <Mus musculus>, Mouse, House Mice, Swiss Mice, house mouse, Mice, Laboratory Mouse, House Mouse, mice C57BL/6xCBA/CaJ hybrid, domesticus, Mus muscarisfalseMus musculusTumor circulating DNA profiling in xenografted mice exposed to intermittent hypoxia2025-09-242015-02-26PRJNA260179GSE61070100902648421425415227