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

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)29795-29807
Number of pages13
JournalOncotarget
Volume6
Issue number30
DOIs
StatePublished - 2015

Fingerprint

Nucleic Acid Repetitive Sequences
Telomere
Plasma Cells
Early Detection of Cancer
Breast Neoplasms
DNA
Telomere Shortening
Polymerase Chain Reaction
Biomarkers
Carcinoma, Intraductal, Noninfiltrating
Neoplasms
Sensitivity and Specificity

Keywords

  • Breast cancer
  • Early cancer detection
  • Plasma cell-free DNA
  • Real-time qPCR
  • Telomere

ASJC Scopus subject areas

  • Oncology

Cite this

Aberrant reduction of telomere repetitive sequences in plasma cell-free DNA for early breast cancer detection. / Wu, Xi; Tanaka, Hiromi.

In: Oncotarget, Vol. 6, No. 30, 2015, p. 29795-29807.

Research output: Contribution to journalArticle

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