Research Papers:

A plasma telomeric cell-free DNA level in unaffected women with BRCA1 or/and BRCA2 mutations: a pilot study

Shatovisha Dey, Natascia Marino, Kanokwan Bishop, Paige N. Dahlgren, Aditi Shendre, Anna Maria Storniolo, Chunyan He and Hiromi Tanaka _

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Oncotarget. 2018; 9:4214-4222. https://doi.org/10.18632/oncotarget.23767

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Shatovisha Dey1, Natascia Marino2,3, Kanokwan Bishop1, Paige N. Dahlgren1, Aditi Shendre4, Anna Maria Storniolo2,3, Chunyan He5 and Hiromi Tanaka1

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

2Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

3Susan G. Komen Tissue Bank at IU Simon Cancer Center, Indianapolis, IN, USA

4Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA

5Department of Internal Medicine, College of Medicine, Markey Cancer Center, University of Kentucky, Lexington, KY, USA

Correspondence to:

Hiromi Tanaka, email: [email protected]

Keywords: BRCA1; BRCA2; telomere; circulating cell-free DNA; qPCR

Received: November 03, 2017     Accepted: December 21, 2017     Published: December 29, 2017


Plasma cell-free DNA (cfDNA) is a small DNA fragment circulating in the bloodstream originating from both non-tumor- and tumor-derived cells. A previous study showed that a plasma telomeric cfDNA level decreases in sporadic breast cancer patients compared to controls. Tumor suppressor gene products including BRCA1 and BRCA2 (BRCA1&2) play an important role in telomere maintenance. In this study, we hypothesized that the plasma telomeric cfDNA level is associated with the mutation status of BRCA1&2 genes. To test this hypothesis, we performed plasma telomeric cfDNA quantitative PCR (qPCR)-based assays to compare 28 women carriers of the BRCA1&2 mutation with age-matched controls of 28 healthy women. The results showed that the plasma telomeric cfDNA level was lower in unaffected BRCA1&2 mutation carriers than in age-matched controls from non-obese women (BMI < 30), while there was no association between unaffected BRCA1&2 mutation carriers and age-matched controls in obese women (BMI > 30). Moreover, the plasma telomeric cfDNA level applied aptly to the Tyrer-Cuzick model in non-obese women. These findings suggest that circulating cfDNA may detect dysfunctional telomeres derived from cells with BRCA1&2 mutations and, therefore, its level is associated with breast cancer susceptibility. This pilot study warrants further investigation to elucidate the implication of plasma telomeric cfDNA levels in relation to cancer and obesity.

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