Aberrant reduction of telomere repetitive sequences in plasma cell-free DNA for early breast cancer detection.

dc.contributor.authorWu, Xi
dc.contributor.authorTanaka, Hiromi
dc.contributor.departmentDepartment of Medical & Molecular Genetics, IU School of Medicineen_US
dc.date.accessioned2016-03-31T15:34:44Z
dc.date.available2016-03-31T15:34:44Z
dc.date.issued2015-10-06
dc.description.abstractExcessive telomere shortening is observed in breast cancer lesions when compared to adjacent non-cancerous tissues, suggesting that telomere length may represent a key biomarker for early cancer detection. Because tumor-derived, cell-free DNA (cfDNA) is often released from cancer cells and circulates in the bloodstream, we hypothesized that breast cancer development is associated with changes in the amount of telomeric cfDNA that can be detected in the plasma. To test this hypothesis, we devised a novel, highly sensitive and specific quantitative PCR (qPCR) assay, termed telomeric cfDNA qPCR, to quantify plasma telomeric cfDNA levels. Indeed, the internal reference primers of our design correctly reflected input cfDNA amount (R2 = 0.910, P = 7.82 × 10−52), implying accuracy of this assay. We found that plasma telomeric cfDNA levels decreased with age in healthy individuals (n = 42, R2 = 0.094, P = 0.048), suggesting that cfDNA is likely derived from somatic cells in which telomere length shortens with increasing age. Our results also showed a significant decrease in telomeric cfDNA level from breast cancer patients with no prior treatment (n = 47), compared to control individuals (n = 42) (P = 4.06 × 10−8). The sensitivity and specificity for the telomeric cfDNA qPCR assay was 91.49% and 76.19%, respectively. Furthermore, the telomeric cfDNA level distinguished even the Ductal Carcinoma In Situ (DCIS) group (n = 7) from the healthy group (n = 42) (P = 1.51 × 10−3). Taken together, decreasing plasma telomeric cfDNA levels could be an informative genetic biomarker for early breast cancer detection.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationWu, X., & Tanaka, H. (2015). Aberrant reduction of telomere repetitive sequences in plasma cell-free DNA for early breast cancer detection. Oncotarget, 6(30), 29795–29807. http://doi.org/10.18632/oncotarget.5083en_US
dc.identifier.issn1949-2553en_US
dc.identifier.urihttps://hdl.handle.net/1805/9147
dc.language.isoen_USen_US
dc.publisherImpact Journalsen_US
dc.relation.isversionof10.18632/oncotarget.5083en_US
dc.relation.journalOncotargeten_US
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjecttelomereen_US
dc.subjectplasma cell-free DNAen_US
dc.subjectbreast canceren_US
dc.subjectearly cancer detectionen_US
dc.subjectreal-time qPCRen_US
dc.titleAberrant reduction of telomere repetitive sequences in plasma cell-free DNA for early breast cancer detection.en_US
dc.typeArticleen_US
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