Scientific Rationale

BARD1 is potentially both a diagnostic biomarker and therapeutic target for cancer.

Diagnostic Biomarker

BARD1 protein has important properties that make it attractive for cancer diagnosis:

  • Aberrant BARD1 proteins are released (ie outside the cell body) in large amounts by cancer cells[1][4], and thus give rise to the generation of circulating antibodies. These circulating antibodies are present early in the blood and are therefore easily accessible markers of cancer.
  • BARD1 epitopes are immunogenic[5] and BARD1’s diagnostic tests exploit the presence of these circulating antibodies, which serve as “biomarkers” for the announcement and progression of cancer cells.
  • BARD1 cancer-specific RNA-isoforms are generated by alternate splicing of the BARD1 gene[1][4]. This leads to RNA-based “signatures” that are diagnostic of cancer. These can be addressed in liquid biopsies by analysing Circulating Tumour Cells (CTC) and/or circulating RNA.


Therapeutic Target

The oncogenic capacity of cancer-associated BARD1 isoforms makes them potential therapeutic targets that can be addressed using inhibitory approaches based on small interfering RNAs, anti-BARD1 antibodies, or other methods enabling targeted therapies for prevention or treatment of cancer.

[1] Wu, J.Y., A.T. Vlastos, M.F. Pelte, M.A. Caligo, A. Bianco, K.H. Krause, G.J. Laurent, and I. Irminger-Finger. 2006. Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis. Int J Cancer 118: 1215-26.
[2] Li, L., S. Ryser, E. Dizin, D. Pils, M. Krainer, C.E. Jefford, F. Bertoni, R. Zeillinger, and I. Irminger-Finger. 2007b. Oncogenic BARD1 isoforms expressed in gynecological cancers. Cancer Res 67: 11876-85.
[3]  Zhang YQ, Bianco A, Malkinson AM, Leoni VP, Frau G, De Rosa N, André PA, Versace R, Boulvain M, Laurent GJ, Atzori L, Irminger-Finger I. 2012. BARD1: an independent predictor of survival in non-small cell lung cancer. Int J Cancer. 131(1):83-94.
[4] Zhang YQ, Pilyugin M, Kuester D, Leoni VP, Li L, Casula G, Zorcolo L, Schneider-Stock R, Atzori L, Irminger-Finger I. 2012. Expression of oncogenic BARD1 isoforms affects colon cancer progression and correlates with clinical outcome. Br J Cancer 107:675-83.
[5] Gautier, F., I. Irminger-Finger, M. Gregoire, K. Meflah, and J. Harb. 2000. Identification of an apoptotic cleavage product of BARD1 as an autoantigen: a potential factor in the antitumoural response mediated by apoptotic bodies. Cancer Res 60: 6895-900.