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Identification of BRCA1/2 mutation female carriers using circulating microRNA profiles

Author

Listed:
  • Kevin Elias

    (Brigham and Women’s Hospital)

  • Urszula Smyczynska

    (Medical University of Lodz)

  • Konrad Stawiski

    (Medical University of Lodz)

  • Zuzanna Nowicka

    (Medical University of Lodz)

  • James Webber

    (Brigham and Women’s Hospital)

  • Jakub Kaplan

    (Dana-Farber Cancer Institute)

  • Charles Landen

    (University of Virginia)

  • Jan Lubinski

    (International Hereditary Cancer Center of the Pomeranian Medical University)

  • Asima Mukhopadhyay

    (Kolkata Gynecology Oncology Trials and Translational Research Group)

  • Dona Chakraborty

    (Kolkata Gynecology Oncology Trials and Translational Research Group)

  • Denise C. Connolly

    (Fox Chase Cancer Center)

  • Heather Symecko

    (University of Pennsylvania)

  • Susan M. Domchek

    (University of Pennsylvania)

  • Judy E. Garber

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Panagiotis Konstantinopoulos

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Wojciech Fendler

    (Medical University of Lodz
    Dana-Farber Cancer Institute)

  • Dipanjan Chowdhury

    (Dana-Farber Cancer Institute
    Dana-Farber Cancer Institute
    Harvard Medical School)

Abstract

Identifying germline BRCA1/2 mutation carriers is vital for reducing their risk of breast and ovarian cancer. To derive a serum miRNA-based diagnostic test we used samples from 653 healthy women from six international cohorts, including 350 (53.6%) with BRCA1/2 mutations and 303 (46.4%) BRCA1/2 wild-type. All individuals were cancer-free before and at least 12 months after sampling. RNA-sequencing followed by differential expression analysis identified 19 miRNAs significantly associated with BRCA mutations, 10 of which were ultimately used for classification: hsa-miR-20b-5p, hsa-miR-19b-3p, hsa-let-7b-5p, hsa-miR-320b, hsa-miR-139-3p, hsa-miR-30d-5p, hsa-miR-17-5p, hsa-miR-182-5p, hsa-miR-421, hsa-miR-375-3p. The final logistic regression model achieved area under the receiver operating characteristic curve 0.89 (95% CI: 0.87–0.93), 93.88% sensitivity and 80.72% specificity in an independent validation cohort. Mutated gene, menopausal status or having preemptive oophorectomy did not affect classification performance. Circulating microRNAs may be used to identify BRCA1/2 mutations in patients of high risk of cancer, offering an opportunity to reduce screening costs.

Suggested Citation

  • Kevin Elias & Urszula Smyczynska & Konrad Stawiski & Zuzanna Nowicka & James Webber & Jakub Kaplan & Charles Landen & Jan Lubinski & Asima Mukhopadhyay & Dona Chakraborty & Denise C. Connolly & Heathe, 2023. "Identification of BRCA1/2 mutation female carriers using circulating microRNA profiles," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38925-4
    DOI: 10.1038/s41467-023-38925-4
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    References listed on IDEAS

    as
    1. Shailja Pathania & Sangeeta Bade & Morwenna Le Guillou & Karly Burke & Rachel Reed & Christian Bowman-Colin & Ying Su & David T. Ting & Kornelia Polyak & Andrea L. Richardson & Jean Feunteun & Judy E., 2014. "BRCA1 haploinsufficiency for replication stress suppression in primary cells," Nature Communications, Nature, vol. 5(1), pages 1-15, December.
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