Files

658430.pdf (2.52 MB)

Document type

Article

Version

Published version

Publication date

2015-01-01

Publication license

cc-by (c) Cortese, Rene et al., 2015
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/105406

Tumor circulating DNA profiling in xenografted mice exposed to intermittent hypoxia.

Journal Title

Authors

Director/Tutor

Journal ISSN

Volume Title

Related resource

https://doi.org/10.18632/oncotarget.2785

Abstract

Intermittent hypoxia (IH) a hallmark characteristic of obstructive sleep apnea (OSA), is proposed as a major determinant of processes involving tumor growth, invasion and metastasis. To examine whether circulating DNA (cirDNA) in blood plasma reflects changes in tumor cells under IH conditions, we used a xenografted murine model. Mice engrafted with TC1 epithelial lung cancer cells 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). Significant associations between plasma cirDNA concentrations and tumor size, weight and invasiveness also emerged (p<0.05). Using a methylation microarray-based approach, we identified 2,094 regions showing significant differential cirDNA modifications. Systems biology analyses revealed an association with molecular pathways deregulated 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. Thus, exposures to IH increase 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.

Subject

Síndromes d'apnea del son, Anoxèmia, Càncer, Reacció en cadena de la polimerasa, Rates (Animals de laboratori)

Subject (English)

Sleep apnea syndromes, Anoxemia, Cancer, Polymerase chain reaction, Rats as laboratory animals

Citation

Collections

Articles publicats en revistes (Biomedicina)

Citation

CORTESE, Rene, et al. Tumor circulating DNA profiling in xenografted mice exposed to intermittent hypoxia. Oncotarget. 2015. Vol. 6, num. 1, pags. 556-569. ISSN 1949-2553. [consulted: 17 of June of 2026]. Available at: https://hdl.handle.net/2445/105406

Export metadata

JSON - METS

Share record