Research Papers:

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

Xi Wu _ and Hiromi Tanaka

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Oncotarget. 2015; 6:29795-29807. https://doi.org/10.18632/oncotarget.5083

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Xi Wu1, Hiromi Tanaka1

1Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA

Correspondence to:

Hiromi Tanaka, e-mail: [email protected]

Keywords: telomere, plasma cell-free DNA, breast cancer, early cancer detection, real-time qPCR

Received: June 09, 2015     Accepted: August 13, 2015     Published: August 24, 2015


Excessive 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.

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